In a recent paper published in the journal (1), we reported results of an ecological multifactori... more In a recent paper published in the journal (1), we reported results of an ecological multifactorial study showing that the growing incidence of prostate cancer in Martinique and Guadeloupe is probably caused by environmental factors, and have hypothesized in a second paper that among factors, spray of organochlorine pesticides might be causally involved (2). Table I indicates the different carcinogenic, mutagenic and/or reprotoxic (CMR) or presumed CMR pesticides used since 1955 in the two islands. Unlike that indicated in our first paper (1), aldrin and dieldrin are not rated as 2B carcinogens but instead as group 3 in the IARC classification. Moreover, although our paper clearly showed an excess of prostate cancer in the South East part of Martinique (Fig. 1), unfortunately in the text, this area was mentioned as corresponding to the SouthWest of the island. These two necessary precisions do not change the basic conclusions of our paper, and the importance of its scientific message, since it clearly establishes for the first time that prostate cancer may be an environmental disease.
Using a transdisciplinary methodological approach we have conducted a multifactorial analysis in ... more Using a transdisciplinary methodological approach we have conducted a multifactorial analysis in Martinique and Guadeloupe in order to elucidate the aetiology of prostate cancer. In 2002, world age standardized rates of prostate cancer were 152 new cases per 100,000 person-years in the two islands; one of the highest worldwide rates and much higher than those reported for other Caribbean islands and metropolitan France. Using a linear regression analysis, we found that the growth curves of incidence rates for Martinique and metropolitan France have been significantly diverging since 1983. That these curves are not parallel suggests that although a Caribbean genetic susceptibility factor may be involved in carcinogenesis, this factor cannot per se account for the observed growing incidence. On the basis of mapping analysis of soil pollution, we further showed that water contamination by pesticides originates from banana plantations. Moreover, we have established retrospectively that general population subjects investigated in 1972 in Martinique for the presence of organochlorinated pesticides in their adipose tissue had been contaminated by extremely high levels of DDT, DDE, •, ß and ÁHCH, aldrin and dieldrin. Our study leads to the conclusion that the growing incidence of prostate cancer cannot be related either to a modification of ethnographic factors nor to a change in lifestyle and therefore suggests that environmental factors such as the intensive and prolonged exposure to carcinogenic, mutagenic and reproductive toxin pesticides may cause prostate cancer.
Environmental carcinogens are physical, chemical, and biological exogenous agents that cause canc... more Environmental carcinogens are physical, chemical, and biological exogenous agents that cause cancer after having penetrated into the organism. Cancer is basically a disease caused by chronic exposure to low-dose carcinogens. Mutagenesis and tumor promotion are rate-limiting steps. Accordingly, carcinogens have been distinguished into mutagens and promoters, albeit complete carcinogens can be both. Oncogenic viruses, radiation, and many xenochemicals are environmental carcinogens acting through specific molecular and cellular pathways. They are, however, also characterized by a set of common general mechanisms including the induction of inflammation, immunosuppression, and hormonal disruption of fetal and neonatal tissues. Molecular mechanisms involve direct DNA alterations leading to mutagenesis and epigenetic alterations through free radical production leading to indirect mutagenesis and tumor promotion. A basic property of chemical environmental carcinogens − for example, polycyclic aromatic hydrocarbons, N-nitroso compounds, aromatic and heterocyclic amines, dioxins, polychlorobiphenyls, and other organochlorines − is their lipophilicity, so they can enter cells, where they can be fully or partially metabolized by the cytochrome P450 system or other enzymes such as peroxidases. These detoxifying enzymes act in addition to phase II conjugating enzymes such as N-acetyl transferases and sulfotransferases. As a result of these metabolic processes, procarcinogens can be either detoxified or activated into reactive carcinogens. It has been shown that adipose tissue can act as a reservoir where environmental carcinogens and procarcinogens can bioaccumulate and from which they can be released in the blood circulation to target peripheral tissues for carcinogenesis. Because they contribute not only to the promoting and cocarcinogenic effects of many environmental pollutants but also to the mutagenic effects of many of them, both the aryl hydrocarbon receptor and the inducible cytochrome P450 systems are central in chemical environmental carcinogenesis. Despite the fact that endogenous carcinogens may contribute to the genesis of a limited number of cancers, hypothesis is that the recently observed growing incidence of cancer could be mostly caused by chemical environmental carcinogens.
The increasing incidence of a variety of cancers after the Second World War confronts scientists ... more The increasing incidence of a variety of cancers after the Second World War confronts scientists with the question of their origin. In Western countries, expansion and ageing of the population, as well as progress in cancer detection using new diagnostic and screening tests cannot fully account for the observed growing incidence of cancer. Our hypothesis is that environmental factors play a more important role in cancer genesis than it is usually agreed: i) over the last 2-3 decades, alcohol consumption and tobacco smoking in men have significantly decreased; ii) obesity is increasing in many countries, but the growing incidence of cancer also concerns cancers not related to obesity nor to other lifestyle-related factors; iii) there is evidence that the environment has changed over the same time scale as the recent rise in cancer incidence, and that this change included the accumulation of many new carcinogenic factors in the environment; iv) genetic susceptibility to cancer due to genetic polymorphism cannot have changed over one generation and actually favours the role of exogenous factors through geneenvironment interactions; v) age is not the unique factor to be considered since the rising incidence of cancers is seen across all age categories, including children; vi) the fetus is specifically vulnerable to exogenous factors. A fetal exposure during a critical window period may explain why current epidemiological studies may be negative in adults. We therefore propose that the involuntary exposure to many carcinogens in the environment contributes to the rising trend in cancer incidence.
Prostate and breast cancers have become very frequent in Martinique. We previously conducted a mu... more Prostate and breast cancers have become very frequent in Martinique. We previously conducted a multifactorial analysis in the French Caribbean Island, Martinique, in order to elucidate the aetiology of prostate cancer. Using a linear regression analysis, we found that the growth curves of incidence rates for Martinique and metropolitan France have been significantly diverging since 1983. Although a Caribbean genetic susceptibility factor may be involved in prostate carcinogenesis: this factor, because it could not have changed during the observation period, cannot per se account for the growing incidence of this cancer in the island. We therefore suggested that among possible environmental factors, the intensive and prolonged exposure to Carcinogenic, Mutagenic and/or Reprotoxic (CMR) or presumed CMR pesticides may account for the observed growing incidence of prostate cancer and thus may be involved in prostate carcinogenesis. In this study, we further attempt to show that due to their carcinogenic properties, pesticides and especially organochlorine pesticides may in fact be causally implicated in the growing incidence of prostate cancer in Martinique. Also, we suggest that CMR or presumed CMR pesticides may be causally involved in the growing incidence of breast cancer through a common endocrine disruption mechanism. We therefore propose that protective medical recommendations should be immediately set up and carried out by general practitioners, paediatricians, obstetricians, gynaecologists and urologists; and that public health measures of primary precaution and prevention should be urgently taken in close collaboration with health professionals in order to protect population, more especially pregnant women and children, with the final objective perhaps that these medical recommendations and public health measures will stop Martinique's cancer epidemic.
Thank you for your email. I apologise for not responding to your earlier communication, it must h... more Thank you for your email. I apologise for not responding to your earlier communication, it must have gone 'hull down' amongst the hundreds of emails I get each week. I support the petition. I append some papers which we have published in the recent past in connection with cancer and the environment, in evidence. In particular I would like to draw your attention to the paper on the 'cancer temporality index'. I note that one of the responses to the petition wheels out the weary old argument the 'we are getting older and therefore the incidence of cancer must increase', as if simply getting older is the cause of the cancer. Of course if you exist in an environment that is full of cancer causing agents/influences, age will be one of the functions associated with cancer because the longer you live the more time such influences have to act. In the cancer temporality index paper we demonstrate that, for some cancers, the average age of incidence is decreasing-people are getting cancer younger. This does not fit in with the 'we are getting older' argument. I hope that these submissions will help the Committee in its deliberations.
We have previously shown that benzo[a]pyrene (B[a]P) administrated at extremely low dose can caus... more We have previously shown that benzo[a]pyrene (B[a]P) administrated at extremely low dose can cause weight gain in mice and that the increase in adipose tissue mass is due to inhibition of beta-adrenergic stimulation of lipolysis. Moreover we have suggested that in addition to its endocrine properties, adipose tissue act as a reservoir for many chemical carcinogens including Polycyclic Aromatic Hydrocarbons (PAHs). In this paper we show that B[a]P as well as the two C4 PAHs, pyrene and phenanthrene can bioaccumulate into adipocytes in a similar manner, but that at the difference of B[a]P, have no impact on epinephrine-induced lipolysis. On the basis of this ex vivo study, we therefore suggest that B[a]P may play a central role in carcinogenesis not only by inducing cancer through its mutagenic properties, but also by increasing the bioaccumulation capacity of the adipose tissue mass.
JNCI Journal of the National Cancer Institute, 2010
ABSTRACT levels considerably higher than those in 1986. Overall incidence, however, obscured dist... more ABSTRACT levels considerably higher than those in 1986. Overall incidence, however, obscured distinct age-specific patterns: The relative incidence rate (2005 relative to 1986) was 0.56 in men aged 80 years and older, 1.09 in men aged 70 - 79 years, 1.91 in men aged 60 - 69 years, 3.64 in men aged 50 - 59 years, and 7.23 in men younger than 50 years. Since 1986, an estimated additional 1 305 600 men were diagnosed with prostate cancer, 1 004 800 of whom were definitively treated for the disease. Using the most optimistic assumption about the benefit of screening — that the entire decline in prostate cancer mortality observed during this period is attributable to this additional diagnosis — we estimated that, for each man who experienced the presumed benefit, more than 20 had to be diagnosed with prostate cancer. Conclusions The introduction of PSA screening has resulted in more than 1 million additional men being diagnosed and treated for prostate cancer in the United States. The growth is particularly dramatic for younger men. Given the considerable time that has passed since PSA screening began, most of this excess incidence must represent overdiagnosis.
Due to their lipophilic properties, dioxins can be integrated into the lipidic vacuole of adipocy... more Due to their lipophilic properties, dioxins can be integrated into the lipidic vacuole of adipocytes (fat cells). The aim of this study was to determine the kinetics of incorporation and release of 3H-labelled palmitic acid and 14C-labelled 2,3,7,8-TCDD in isolated adipocytes from pigs. The incorporation of 2,3,7,8-TCDD and palmitic acid was found to be concomitant under conditions of lipogenesis, under the effect of increasing quantities of insulin and in the presence of glucose. Release of these two compounds was found to be dependant on a lipolytic agent (epinephrine). These results suggest the risk of a strong increase of 2,3,7,8-TCDD, induced by lipolysis, in the blood of animals or humans previously exposed to this dioxin.
We have recently proposed that lifestyle-related factors, screening and aging cannot fully accoun... more We have recently proposed that lifestyle-related factors, screening and aging cannot fully account for the present overall growing incidence of cancer. In order to propose the concept that in addition to lifestyle related factors, exogenous environmental factors may play a more important role in carcinogenesis than it is expected, and may therefore account for the growing incidence of cancer, we overview herein environmental factors, rated as certainly or potentially carcinogenic by the International Agency for Research on Cancer (IARC). We thus analyze the carcinogenic effect of microorganisms (including viruses), radiations (including radioactivity, UV and pulsed electromagnetic fields) and xenochemicals. Chemicals related to environmental pollution appear to be of critical importance, since they can induce occupational cancers as well as other cancers. Of major concerns are: outdoor air pollution by carbon particles associated with polycyclic aromatic hydrocarbons; indoor air pollution by environmental tobacco smoke, formaldehyde and volatile organic compounds such as benzene and 1,3 butadiene, which may particularly affect children, and food pollution by food additives and by carcinogenic contaminants such as nitrates, pesticides, dioxins and other organochlorines. In addition, carcinogenic metals and metalloids, pharmaceutical medicines and cosmetics may be involved. Although the risk fraction attributable to environmental factors is still unknown, this long list of carcinogenic and especially mutagenic factors supports our working hypothesis according to which numerous cancers may in fact be caused by the recent modification of our environment.
Exogenous chemical carcinogenesis is an extremely complex multifactorial process during which gen... more Exogenous chemical carcinogenesis is an extremely complex multifactorial process during which gene-environment interactions involving chronic exposure to exogenous chemical carcinogens (ECCs) and polymorphisms of cancer susceptibility genes add further complexity. We describe the properties and molecular mechanisms of ECCs that contribute to induce and generate cancer. A basic and specific property of many lipophilic organic ECCs including polycyclic aromatic hydrocarbons and polyhalogenated aromatic hydrocarbons is their ability to bioaccumulate in the adipose tissue from where they may be released in the blood circulation and target peripheral tissues for carcinogenesis. Many organic ECCs are procarcinogens and consequently need to be activated by the cytochrome P450 (CYP) system and/or other enzymes before they can adduct DNA and proteins. Because they contribute not only to the cocarcinogenic and promoting effects of many aromatic pollutants but also to their mutagenic effects, the aryl hydrocarbon receptor-activating and the inducible CYP systems are central to exogenous chemical carcinogenesis. Another basic property of ECCs is their ability to induce stable and bulky DNA adducts that cannot be simply repaired by the different repair systems. In addition, following ECC exposure, mutagenesis may also be caused indirectly by free-radical production and by epigenetic alterations. As a result of complex molecular interplays, direct and/or indirect mutagenesis may especially account for the carcinogenic effects of many exogenous metals and metalloids. Because of these molecular properties and action mechanisms, we conclude that ECCs could be major contributors to human cancer, with obviously great public health consequences.
The classical view according to which overweight/obesity is related to cancer considers adipose t... more The classical view according to which overweight/obesity is related to cancer considers adipose tissue as an active and metabolic "organ", acting through endocrine, autocrine and paracrine processes. Consequently, it has been hypothesized, that genesis and progression of cancer may be caused by different biological factors acting through diverse mechanisms including changes in the synthesis and bioavailability of sex hormones, insulin resistance, release of growth factors and/or proinflammatory cytokines and abnormal energetic disposal and expenditure. We have shown that overweight/obesity can be experimentally induced by benzo[a]pyrene, a universal well characterized chemical pollutant and that overweight/obesity may in fact be caused by several types of chemical pollutants. In this paper we propose that in addition to the above hypothetical biological mechanisms, adipose tissue acts as a reservoir for lipophilic, liposoluble environmental carcinogens, so that chemical pollution may in fact generate both overweight/obesity and cancer. More precisely, we propose that many carcinogens, be they mutagens or promotors can be stored in the adipose tissue, be released at convenient dose in the blood circulation and therefore target peripheral tissues to induce carcinogenesis. Such carcinogens mainly include organochlorine pesticides and PCBs. Their association with an increased risk of cancer seems to be demonstrated for breast and prostate carcinoma, as well as for lymphoma, not only in obese patients, but also in normal weight or even leaner patients suggesting that the adipose tissue may act as a reservoir for environmental carcinogens in obese as well as in non-obese patients.
In a recent paper published in the journal (1), we reported results of an ecological multifactori... more In a recent paper published in the journal (1), we reported results of an ecological multifactorial study showing that the growing incidence of prostate cancer in Martinique and Guadeloupe is probably caused by environmental factors, and have hypothesized in a second paper that among factors, spray of organochlorine pesticides might be causally involved (2). Table I indicates the different carcinogenic, mutagenic and/or reprotoxic (CMR) or presumed CMR pesticides used since 1955 in the two islands. Unlike that indicated in our first paper (1), aldrin and dieldrin are not rated as 2B carcinogens but instead as group 3 in the IARC classification. Moreover, although our paper clearly showed an excess of prostate cancer in the South East part of Martinique (Fig. 1), unfortunately in the text, this area was mentioned as corresponding to the SouthWest of the island. These two necessary precisions do not change the basic conclusions of our paper, and the importance of its scientific message, since it clearly establishes for the first time that prostate cancer may be an environmental disease.
Using a transdisciplinary methodological approach we have conducted a multifactorial analysis in ... more Using a transdisciplinary methodological approach we have conducted a multifactorial analysis in Martinique and Guadeloupe in order to elucidate the aetiology of prostate cancer. In 2002, world age standardized rates of prostate cancer were 152 new cases per 100,000 person-years in the two islands; one of the highest worldwide rates and much higher than those reported for other Caribbean islands and metropolitan France. Using a linear regression analysis, we found that the growth curves of incidence rates for Martinique and metropolitan France have been significantly diverging since 1983. That these curves are not parallel suggests that although a Caribbean genetic susceptibility factor may be involved in carcinogenesis, this factor cannot per se account for the observed growing incidence. On the basis of mapping analysis of soil pollution, we further showed that water contamination by pesticides originates from banana plantations. Moreover, we have established retrospectively that general population subjects investigated in 1972 in Martinique for the presence of organochlorinated pesticides in their adipose tissue had been contaminated by extremely high levels of DDT, DDE, •, ß and ÁHCH, aldrin and dieldrin. Our study leads to the conclusion that the growing incidence of prostate cancer cannot be related either to a modification of ethnographic factors nor to a change in lifestyle and therefore suggests that environmental factors such as the intensive and prolonged exposure to carcinogenic, mutagenic and reproductive toxin pesticides may cause prostate cancer.
Environmental carcinogens are physical, chemical, and biological exogenous agents that cause canc... more Environmental carcinogens are physical, chemical, and biological exogenous agents that cause cancer after having penetrated into the organism. Cancer is basically a disease caused by chronic exposure to low-dose carcinogens. Mutagenesis and tumor promotion are rate-limiting steps. Accordingly, carcinogens have been distinguished into mutagens and promoters, albeit complete carcinogens can be both. Oncogenic viruses, radiation, and many xenochemicals are environmental carcinogens acting through specific molecular and cellular pathways. They are, however, also characterized by a set of common general mechanisms including the induction of inflammation, immunosuppression, and hormonal disruption of fetal and neonatal tissues. Molecular mechanisms involve direct DNA alterations leading to mutagenesis and epigenetic alterations through free radical production leading to indirect mutagenesis and tumor promotion. A basic property of chemical environmental carcinogens − for example, polycyclic aromatic hydrocarbons, N-nitroso compounds, aromatic and heterocyclic amines, dioxins, polychlorobiphenyls, and other organochlorines − is their lipophilicity, so they can enter cells, where they can be fully or partially metabolized by the cytochrome P450 system or other enzymes such as peroxidases. These detoxifying enzymes act in addition to phase II conjugating enzymes such as N-acetyl transferases and sulfotransferases. As a result of these metabolic processes, procarcinogens can be either detoxified or activated into reactive carcinogens. It has been shown that adipose tissue can act as a reservoir where environmental carcinogens and procarcinogens can bioaccumulate and from which they can be released in the blood circulation to target peripheral tissues for carcinogenesis. Because they contribute not only to the promoting and cocarcinogenic effects of many environmental pollutants but also to the mutagenic effects of many of them, both the aryl hydrocarbon receptor and the inducible cytochrome P450 systems are central in chemical environmental carcinogenesis. Despite the fact that endogenous carcinogens may contribute to the genesis of a limited number of cancers, hypothesis is that the recently observed growing incidence of cancer could be mostly caused by chemical environmental carcinogens.
The increasing incidence of a variety of cancers after the Second World War confronts scientists ... more The increasing incidence of a variety of cancers after the Second World War confronts scientists with the question of their origin. In Western countries, expansion and ageing of the population, as well as progress in cancer detection using new diagnostic and screening tests cannot fully account for the observed growing incidence of cancer. Our hypothesis is that environmental factors play a more important role in cancer genesis than it is usually agreed: i) over the last 2-3 decades, alcohol consumption and tobacco smoking in men have significantly decreased; ii) obesity is increasing in many countries, but the growing incidence of cancer also concerns cancers not related to obesity nor to other lifestyle-related factors; iii) there is evidence that the environment has changed over the same time scale as the recent rise in cancer incidence, and that this change included the accumulation of many new carcinogenic factors in the environment; iv) genetic susceptibility to cancer due to genetic polymorphism cannot have changed over one generation and actually favours the role of exogenous factors through geneenvironment interactions; v) age is not the unique factor to be considered since the rising incidence of cancers is seen across all age categories, including children; vi) the fetus is specifically vulnerable to exogenous factors. A fetal exposure during a critical window period may explain why current epidemiological studies may be negative in adults. We therefore propose that the involuntary exposure to many carcinogens in the environment contributes to the rising trend in cancer incidence.
Prostate and breast cancers have become very frequent in Martinique. We previously conducted a mu... more Prostate and breast cancers have become very frequent in Martinique. We previously conducted a multifactorial analysis in the French Caribbean Island, Martinique, in order to elucidate the aetiology of prostate cancer. Using a linear regression analysis, we found that the growth curves of incidence rates for Martinique and metropolitan France have been significantly diverging since 1983. Although a Caribbean genetic susceptibility factor may be involved in prostate carcinogenesis: this factor, because it could not have changed during the observation period, cannot per se account for the growing incidence of this cancer in the island. We therefore suggested that among possible environmental factors, the intensive and prolonged exposure to Carcinogenic, Mutagenic and/or Reprotoxic (CMR) or presumed CMR pesticides may account for the observed growing incidence of prostate cancer and thus may be involved in prostate carcinogenesis. In this study, we further attempt to show that due to their carcinogenic properties, pesticides and especially organochlorine pesticides may in fact be causally implicated in the growing incidence of prostate cancer in Martinique. Also, we suggest that CMR or presumed CMR pesticides may be causally involved in the growing incidence of breast cancer through a common endocrine disruption mechanism. We therefore propose that protective medical recommendations should be immediately set up and carried out by general practitioners, paediatricians, obstetricians, gynaecologists and urologists; and that public health measures of primary precaution and prevention should be urgently taken in close collaboration with health professionals in order to protect population, more especially pregnant women and children, with the final objective perhaps that these medical recommendations and public health measures will stop Martinique's cancer epidemic.
Thank you for your email. I apologise for not responding to your earlier communication, it must h... more Thank you for your email. I apologise for not responding to your earlier communication, it must have gone 'hull down' amongst the hundreds of emails I get each week. I support the petition. I append some papers which we have published in the recent past in connection with cancer and the environment, in evidence. In particular I would like to draw your attention to the paper on the 'cancer temporality index'. I note that one of the responses to the petition wheels out the weary old argument the 'we are getting older and therefore the incidence of cancer must increase', as if simply getting older is the cause of the cancer. Of course if you exist in an environment that is full of cancer causing agents/influences, age will be one of the functions associated with cancer because the longer you live the more time such influences have to act. In the cancer temporality index paper we demonstrate that, for some cancers, the average age of incidence is decreasing-people are getting cancer younger. This does not fit in with the 'we are getting older' argument. I hope that these submissions will help the Committee in its deliberations.
We have previously shown that benzo[a]pyrene (B[a]P) administrated at extremely low dose can caus... more We have previously shown that benzo[a]pyrene (B[a]P) administrated at extremely low dose can cause weight gain in mice and that the increase in adipose tissue mass is due to inhibition of beta-adrenergic stimulation of lipolysis. Moreover we have suggested that in addition to its endocrine properties, adipose tissue act as a reservoir for many chemical carcinogens including Polycyclic Aromatic Hydrocarbons (PAHs). In this paper we show that B[a]P as well as the two C4 PAHs, pyrene and phenanthrene can bioaccumulate into adipocytes in a similar manner, but that at the difference of B[a]P, have no impact on epinephrine-induced lipolysis. On the basis of this ex vivo study, we therefore suggest that B[a]P may play a central role in carcinogenesis not only by inducing cancer through its mutagenic properties, but also by increasing the bioaccumulation capacity of the adipose tissue mass.
JNCI Journal of the National Cancer Institute, 2010
ABSTRACT levels considerably higher than those in 1986. Overall incidence, however, obscured dist... more ABSTRACT levels considerably higher than those in 1986. Overall incidence, however, obscured distinct age-specific patterns: The relative incidence rate (2005 relative to 1986) was 0.56 in men aged 80 years and older, 1.09 in men aged 70 - 79 years, 1.91 in men aged 60 - 69 years, 3.64 in men aged 50 - 59 years, and 7.23 in men younger than 50 years. Since 1986, an estimated additional 1 305 600 men were diagnosed with prostate cancer, 1 004 800 of whom were definitively treated for the disease. Using the most optimistic assumption about the benefit of screening — that the entire decline in prostate cancer mortality observed during this period is attributable to this additional diagnosis — we estimated that, for each man who experienced the presumed benefit, more than 20 had to be diagnosed with prostate cancer. Conclusions The introduction of PSA screening has resulted in more than 1 million additional men being diagnosed and treated for prostate cancer in the United States. The growth is particularly dramatic for younger men. Given the considerable time that has passed since PSA screening began, most of this excess incidence must represent overdiagnosis.
Due to their lipophilic properties, dioxins can be integrated into the lipidic vacuole of adipocy... more Due to their lipophilic properties, dioxins can be integrated into the lipidic vacuole of adipocytes (fat cells). The aim of this study was to determine the kinetics of incorporation and release of 3H-labelled palmitic acid and 14C-labelled 2,3,7,8-TCDD in isolated adipocytes from pigs. The incorporation of 2,3,7,8-TCDD and palmitic acid was found to be concomitant under conditions of lipogenesis, under the effect of increasing quantities of insulin and in the presence of glucose. Release of these two compounds was found to be dependant on a lipolytic agent (epinephrine). These results suggest the risk of a strong increase of 2,3,7,8-TCDD, induced by lipolysis, in the blood of animals or humans previously exposed to this dioxin.
We have recently proposed that lifestyle-related factors, screening and aging cannot fully accoun... more We have recently proposed that lifestyle-related factors, screening and aging cannot fully account for the present overall growing incidence of cancer. In order to propose the concept that in addition to lifestyle related factors, exogenous environmental factors may play a more important role in carcinogenesis than it is expected, and may therefore account for the growing incidence of cancer, we overview herein environmental factors, rated as certainly or potentially carcinogenic by the International Agency for Research on Cancer (IARC). We thus analyze the carcinogenic effect of microorganisms (including viruses), radiations (including radioactivity, UV and pulsed electromagnetic fields) and xenochemicals. Chemicals related to environmental pollution appear to be of critical importance, since they can induce occupational cancers as well as other cancers. Of major concerns are: outdoor air pollution by carbon particles associated with polycyclic aromatic hydrocarbons; indoor air pollution by environmental tobacco smoke, formaldehyde and volatile organic compounds such as benzene and 1,3 butadiene, which may particularly affect children, and food pollution by food additives and by carcinogenic contaminants such as nitrates, pesticides, dioxins and other organochlorines. In addition, carcinogenic metals and metalloids, pharmaceutical medicines and cosmetics may be involved. Although the risk fraction attributable to environmental factors is still unknown, this long list of carcinogenic and especially mutagenic factors supports our working hypothesis according to which numerous cancers may in fact be caused by the recent modification of our environment.
Exogenous chemical carcinogenesis is an extremely complex multifactorial process during which gen... more Exogenous chemical carcinogenesis is an extremely complex multifactorial process during which gene-environment interactions involving chronic exposure to exogenous chemical carcinogens (ECCs) and polymorphisms of cancer susceptibility genes add further complexity. We describe the properties and molecular mechanisms of ECCs that contribute to induce and generate cancer. A basic and specific property of many lipophilic organic ECCs including polycyclic aromatic hydrocarbons and polyhalogenated aromatic hydrocarbons is their ability to bioaccumulate in the adipose tissue from where they may be released in the blood circulation and target peripheral tissues for carcinogenesis. Many organic ECCs are procarcinogens and consequently need to be activated by the cytochrome P450 (CYP) system and/or other enzymes before they can adduct DNA and proteins. Because they contribute not only to the cocarcinogenic and promoting effects of many aromatic pollutants but also to their mutagenic effects, the aryl hydrocarbon receptor-activating and the inducible CYP systems are central to exogenous chemical carcinogenesis. Another basic property of ECCs is their ability to induce stable and bulky DNA adducts that cannot be simply repaired by the different repair systems. In addition, following ECC exposure, mutagenesis may also be caused indirectly by free-radical production and by epigenetic alterations. As a result of complex molecular interplays, direct and/or indirect mutagenesis may especially account for the carcinogenic effects of many exogenous metals and metalloids. Because of these molecular properties and action mechanisms, we conclude that ECCs could be major contributors to human cancer, with obviously great public health consequences.
The classical view according to which overweight/obesity is related to cancer considers adipose t... more The classical view according to which overweight/obesity is related to cancer considers adipose tissue as an active and metabolic "organ", acting through endocrine, autocrine and paracrine processes. Consequently, it has been hypothesized, that genesis and progression of cancer may be caused by different biological factors acting through diverse mechanisms including changes in the synthesis and bioavailability of sex hormones, insulin resistance, release of growth factors and/or proinflammatory cytokines and abnormal energetic disposal and expenditure. We have shown that overweight/obesity can be experimentally induced by benzo[a]pyrene, a universal well characterized chemical pollutant and that overweight/obesity may in fact be caused by several types of chemical pollutants. In this paper we propose that in addition to the above hypothetical biological mechanisms, adipose tissue acts as a reservoir for lipophilic, liposoluble environmental carcinogens, so that chemical pollution may in fact generate both overweight/obesity and cancer. More precisely, we propose that many carcinogens, be they mutagens or promotors can be stored in the adipose tissue, be released at convenient dose in the blood circulation and therefore target peripheral tissues to induce carcinogenesis. Such carcinogens mainly include organochlorine pesticides and PCBs. Their association with an increased risk of cancer seems to be demonstrated for breast and prostate carcinoma, as well as for lymphoma, not only in obese patients, but also in normal weight or even leaner patients suggesting that the adipose tissue may act as a reservoir for environmental carcinogens in obese as well as in non-obese patients.
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Papers by P. Irigaray