Taking into consideration that glutatione S-transferase (GST) and cellular proliferation play a c... more Taking into consideration that glutatione S-transferase (GST) and cellular proliferation play a crucial role during carcinogenesis, the goal of this study was to investigate the expression of placental GST, called GST-P, and proliferating cellular nuclear antigen (PCNA) by means of immunohistochemistry during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4NQO). This is a useful model for studying oral squamous cell carcinoma phase by phase. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution by drinking water for 4, 12 or 20 weeks. Ten animals were used as negative control. GST-P positive foci were detected in non-neoplastic oral cells at 4 weeks of 4NQO administration. In the same way, GST-P positive cells were detected in pre-neoplastic lesions and squamous cell carcinomas induced after 12 and 20 weeks-treatment, respectively. None of the control animals expressed GST-P positive cells. Regarding cellular proliferation, PCNA positive nuclei were higher at 12 and 20 weeks following 4NQO exposure (po0.05) when compared to negative control. These results suggest that the expression of GST-P is correlated with cellular proliferation, in which GST-P is associated with risk and progression of oral cancer, whereas PCNA is closely involved during neoplastic conversion. r
4-Nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis is a useful model for studying ... more 4-Nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis is a useful model for studying oral squamous cell carcinoma. The aim of this study was to investigate the level of DNA damage induced by 4NQO in oral mucosa cells by the single cell gel (comet) assay. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution by drinking water for 4, 12 or 20 weeks. Ten animals were used as negative control. Statistically significant increase of DNA damage was observed in non-neoplastic oral cells at four weeks of 4NQO administration when compared with control (P < 0.05). The level of DNA damage was directly associated with the severity of histological changes. The results suggest that histologically normal tissue is able to harbor genetically unstable cells contributing to the initiation of oral carcinogenesis. Genomic instability appears to be associated with the risk and progression of oral cancer.
The monoterpene oxide, 1,8-cineole (cineole, eucalyptol) was examined for its possible influence ... more The monoterpene oxide, 1,8-cineole (cineole, eucalyptol) was examined for its possible influence on the acute phase of trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. The test compound, 1,8-cineole (200 and 400 mg/kg) or vehicle (1 ml, 2% Tween 80) was instilled rectally, 24, and 2 h before (pre-treatment) or 2 and 24 h after (post-treatment) the induction of colitis by intracolonic administration of TNBS (0.25 ml of 25 mg of TNBS in 50% ethanol). Rats were killed 48 h after colitis induction and colonic segments were analysed for gross damage scores, changes in wet weights, myeloperoxidase activity, an indicator of neutrophilic infiltration and glutathione level, a major cellular antioxidant. TNBS induced an extensive inflammation and ulceration in the colon. Colonic damage was associated with an increase in myeloperoxidase activity and by a decrease in glutathione. When compared to vehicle-treated TNBS controls, a marked reduction in gross damage scores and wet weights (mg/cm) of colonic segments were evident in animals pre-treated but not post-treated with 1,8-cineole. Cineole also significantly reduced the myeloperoxidase activity, and caused repletion of glutathione. These results confirm the anti-inflammatory action of 1,8-cineole and suggest its potential value as a dietary flavoring agent in the prevention of gastrointestinal inflammation and ulceration.
Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2005
The Caí River (Rio Grande do Sul, Brazil) is an important watercourse that receives large amounts... more The Caí River (Rio Grande do Sul, Brazil) is an important watercourse that receives large amounts of industrial and untreated municipal discharges in its lower course. We employed the SMART in Drosophila melanogaster to evaluate the genotoxicity of surface waters collected from Caí sites receiving direct sewage discharge: from Montenegro (Km 52) and from São Sebastião do Caí (Km 78 and 80), and from two sites under the industrial influence (Km 13.6 and 18.6). The genotoxic analysis included three collections: March, June and September 1999, which were tested at crude sample and at 50 and 25% concentrations. Considering the industrial samples from Km 18.6 and 13.6, collected in March, June and September 1999, they were characterized as not having genetic toxicity. The urban samples collected in March-Km 52, 78 and 80-showed a significant increment in the frequencies of total spots. In Km 52 and 78 the genotoxic effect was associated to both mutational and recombinational events, although for Km 80 the increases observed were mainly related to the occurrence of homologous recombination. Moreover, the Km 80 crude sample from June and all the concentrations analyzed for Km 52 in September were also able to induce mitotic recombination. These effects were only observed in the ST cross, demonstrating the genotoxins present in the urban discharges act by direct interaction with the DNA of the somatic cells. The SMART in D. melanogaster was shown to be highly sensitive to detect genotoxic agents present in the aquatic environment, and must be better exploited for monitoring areas under anthropogenic discharges.
Taking into consideration that glutatione S-transferase (GST) and cellular proliferation play a c... more Taking into consideration that glutatione S-transferase (GST) and cellular proliferation play a crucial role during carcinogenesis, the goal of this study was to investigate the expression of placental GST, called GST-P, and proliferating cellular nuclear antigen (PCNA) by means of immunohistochemistry during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4NQO). This is a useful model for studying oral squamous cell carcinoma phase by phase. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution by drinking water for 4, 12 or 20 weeks. Ten animals were used as negative control. GST-P positive foci were detected in non-neoplastic oral cells at 4 weeks of 4NQO administration. In the same way, GST-P positive cells were detected in pre-neoplastic lesions and squamous cell carcinomas induced after 12 and 20 weeks-treatment, respectively. None of the control animals expressed GST-P positive cells. Regarding cellular proliferation, PCNA positive nuclei were higher at 12 and 20 weeks following 4NQO exposure (po0.05) when compared to negative control. These results suggest that the expression of GST-P is correlated with cellular proliferation, in which GST-P is associated with risk and progression of oral cancer, whereas PCNA is closely involved during neoplastic conversion. r
4-Nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis is a useful model for studying ... more 4-Nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis is a useful model for studying oral squamous cell carcinoma. The aim of this study was to investigate the level of DNA damage induced by 4NQO in oral mucosa cells by the single cell gel (comet) assay. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution by drinking water for 4, 12 or 20 weeks. Ten animals were used as negative control. Statistically significant increase of DNA damage was observed in non-neoplastic oral cells at four weeks of 4NQO administration when compared with control (P < 0.05). The level of DNA damage was directly associated with the severity of histological changes. The results suggest that histologically normal tissue is able to harbor genetically unstable cells contributing to the initiation of oral carcinogenesis. Genomic instability appears to be associated with the risk and progression of oral cancer.
The monoterpene oxide, 1,8-cineole (cineole, eucalyptol) was examined for its possible influence ... more The monoterpene oxide, 1,8-cineole (cineole, eucalyptol) was examined for its possible influence on the acute phase of trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. The test compound, 1,8-cineole (200 and 400 mg/kg) or vehicle (1 ml, 2% Tween 80) was instilled rectally, 24, and 2 h before (pre-treatment) or 2 and 24 h after (post-treatment) the induction of colitis by intracolonic administration of TNBS (0.25 ml of 25 mg of TNBS in 50% ethanol). Rats were killed 48 h after colitis induction and colonic segments were analysed for gross damage scores, changes in wet weights, myeloperoxidase activity, an indicator of neutrophilic infiltration and glutathione level, a major cellular antioxidant. TNBS induced an extensive inflammation and ulceration in the colon. Colonic damage was associated with an increase in myeloperoxidase activity and by a decrease in glutathione. When compared to vehicle-treated TNBS controls, a marked reduction in gross damage scores and wet weights (mg/cm) of colonic segments were evident in animals pre-treated but not post-treated with 1,8-cineole. Cineole also significantly reduced the myeloperoxidase activity, and caused repletion of glutathione. These results confirm the anti-inflammatory action of 1,8-cineole and suggest its potential value as a dietary flavoring agent in the prevention of gastrointestinal inflammation and ulceration.
Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2005
The Caí River (Rio Grande do Sul, Brazil) is an important watercourse that receives large amounts... more The Caí River (Rio Grande do Sul, Brazil) is an important watercourse that receives large amounts of industrial and untreated municipal discharges in its lower course. We employed the SMART in Drosophila melanogaster to evaluate the genotoxicity of surface waters collected from Caí sites receiving direct sewage discharge: from Montenegro (Km 52) and from São Sebastião do Caí (Km 78 and 80), and from two sites under the industrial influence (Km 13.6 and 18.6). The genotoxic analysis included three collections: March, June and September 1999, which were tested at crude sample and at 50 and 25% concentrations. Considering the industrial samples from Km 18.6 and 13.6, collected in March, June and September 1999, they were characterized as not having genetic toxicity. The urban samples collected in March-Km 52, 78 and 80-showed a significant increment in the frequencies of total spots. In Km 52 and 78 the genotoxic effect was associated to both mutational and recombinational events, although for Km 80 the increases observed were mainly related to the occurrence of homologous recombination. Moreover, the Km 80 crude sample from June and all the concentrations analyzed for Km 52 in September were also able to induce mitotic recombination. These effects were only observed in the ST cross, demonstrating the genotoxins present in the urban discharges act by direct interaction with the DNA of the somatic cells. The SMART in D. melanogaster was shown to be highly sensitive to detect genotoxic agents present in the aquatic environment, and must be better exploited for monitoring areas under anthropogenic discharges.
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