MicroGARD 1 200 is a fermented dextrose product used to extend food shelf-life by inhibiting spoi... more MicroGARD 1 200 is a fermented dextrose product used to extend food shelf-life by inhibiting spoilage due to Gram-negative bacteria, selected yeast and molds. The present studies were conducted to evaluate the safety of this food ingredient for determination of GRAS status. MicroGARD 200 was subjected to a bacterial reverse mutation assay, a subchronic oral toxicity study and an oral antigenicity study. It showed no evidence of mutagenic potential or toxicity in four strains of Salmonella typhimurium or in Escherichia coli strain WP2 uvrA with and without metabolic activation. MicroGARD 200 was orally administered to rats for 13 consecutive weeks at dietary concentrations of 0, 0.5, 2.0 or 5.0%. Water consumption and urinary excretion of sodium were slightly increased in both sexes at the high dose due to the sodium content of the test substance (about 6%). Increases in fasting glucose and decreased plasma creatinine were not accompanied by treatment-related histopathological changes and were within the normal range for historical controls. The potential antigenic properties of MicroGARD 200 were investigated via gavage in guinea pigs using an active systemic anaphylaxis (ASA) challenge [Annals of Allergy 67 (1991) 400; Allergy 49 (1994) 361]. There was no evidence of any anaphylactic sensitizing properties for MicroGARD 200.
Our previous data demonstrated that Ras activation is necessary and sucient for transforming grow... more Our previous data demonstrated that Ras activation is necessary and sucient for transforming growth factor b (TGFb)-mediated Erk1 activation, and is partially required for the inhibition of cyclin-dependent kinase 2 (Cdk2) activity, cyclin A expression and DNA synthesis by TGFb (KM Mulder and SL Morris,
Hydroquinone (HQ) exposure is common as it is a natural component of plant-based foods and is use... more Hydroquinone (HQ) exposure is common as it is a natural component of plant-based foods and is used in some fingernail polishes, hair dyes, and skin lighteners. Industrially it is used as an antioxidant, polymerization inhibitor, and reducing agent. The current study was undertaken to determine whether HQ may cause DNA damage in an in vivo comet assay in F344 rats. DNA strand breaks were assessed in the duodenum as a direct tissue contact site, the testes, and the liver and kidneys, which were tumor sites in bioassays. Rats were exposed to HQ by gavage at 0, 105, 210, or 420 mg/kg/day. At all dose levels, mean % tail intensity and tail moment values for all tissues in animals given HQ were similar to the control. There were no statistically significant increases in tail intensity in any tissue following HQ treatment of male and female rat and data for all animals fell within the available historical control ranges for each tissue. There was no evidence of induction of DNA damage in cells isolated from duodenum, kidney or liver of male and female rats or in the testes of male rats following exposure to HQ at a dose levels up to 420 mg/kg/day, which caused acute renal necrosis.
Our previous data demonstrated that Ras activation is necessary and sucient for transforming grow... more Our previous data demonstrated that Ras activation is necessary and sucient for transforming growth factor b (TGFb)-mediated Erk1 activation, and is partially required for the inhibition of cyclin-dependent kinase 2 (Cdk2) activity, cyclin A expression and DNA synthesis by TGFb (KM Mulder and SL Morris,
We have previously demonstrated that growth inhibition of untransformed intestinal epithelial cel... more We have previously demonstrated that growth inhibition of untransformed intestinal epithelial cells by transforming growth factor  1 (TGF) and TGF 2 was associated with a rapid activation of both Ras and extracellular signal-regulated kinase 1 (Erk1) (Mulder, K.
Fifty percent of human colon carcinomas contain activating mutations in the K-ras gene. However, ... more Fifty percent of human colon carcinomas contain activating mutations in the K-ras gene. However, whether these alterations in K-ras affect the function of Ras proteins in growth factor (GF) signal transduction is now known. Here we have characterized a previously defined human colon carcinoma cell model system for K-ras gene mutations and for altered levels of Ras protein expression and have examined whether these alterations affect Ras function in GF signal transduction. Sequence analysis of PCR-amplified K-ras gene fragments indicated that among the more aggressive cell lines, four had a normal K-ras sequence, whereas 3 others (isolated from the same human tumor) contained a mutation at codon 13. In contrast, all 7 of the less aggressive cell lines contained a mutation at either codon 12 or 13. In addition to the presence of a K-ras mutation, one cell line expressed higher levels of the K-Ras protein and displayed elevated Ras-GTP loading (in the absence of GF addition) compared with the other cell lines examined. Despite these alterations, the mitogenic GF combination epidermal growth factor + insulin + transferrin resulted in an activation of Ras and extracellular signal-regulated kinase 2. Collectively, our results indicate that the malignant phenotype of the cell lines was not correlated with the presence of K-ras mutations or with higher levels of Ras protein expression. Furthermore, K-ras mutations, high levels of K-Ras protein expression, and elevated Ras-GTP loading, as they occur naturally in human colon carcinomas, do not abolish the function of Ras in GF signaling.
Hydroquinone (HQ) exposure is common as it is a natural component of plant-based foods and is use... more Hydroquinone (HQ) exposure is common as it is a natural component of plant-based foods and is used in some fingernail polishes, hair dyes, and skin lighteners. Industrially it is used as an antioxidant, polymerization inhibitor, and reducing agent. The current study was undertaken to determine whether HQ may cause DNA damage in an in vivo comet assay in F344 rats. DNA strand breaks were assessed in the duodenum as a direct tissue contact site, the testes, and the liver and kidneys, which were tumor sites in bioassays. Rats were exposed to HQ by gavage at 0, 105, 210, or 420 mg/kg/day. At all dose levels, mean % tail intensity and tail moment values for all tissues in animals given HQ were similar to the control. There were no statistically significant increases in tail intensity in any tissue following HQ treatment of male and female rat and data for all animals fell within the available historical control ranges for each tissue. There was no evidence of induction of DNA damage in cells isolated from duodenum, kidney or liver of male and female rats or in the testes of male rats following exposure to HQ at a dose levels up to 420 mg/kg/day, which caused acute renal necrosis.
MicroGARD 1 200 is a fermented dextrose product used to extend food shelf-life by inhibiting spoi... more MicroGARD 1 200 is a fermented dextrose product used to extend food shelf-life by inhibiting spoilage due to Gram-negative bacteria, selected yeast and molds. The present studies were conducted to evaluate the safety of this food ingredient for determination of GRAS status. MicroGARD 200 was subjected to a bacterial reverse mutation assay, a subchronic oral toxicity study and an oral antigenicity study. It showed no evidence of mutagenic potential or toxicity in four strains of Salmonella typhimurium or in Escherichia coli strain WP2 uvrA with and without metabolic activation. MicroGARD 200 was orally administered to rats for 13 consecutive weeks at dietary concentrations of 0, 0.5, 2.0 or 5.0%. Water consumption and urinary excretion of sodium were slightly increased in both sexes at the high dose due to the sodium content of the test substance (about 6%). Increases in fasting glucose and decreased plasma creatinine were not accompanied by treatment-related histopathological changes and were within the normal range for historical controls. The potential antigenic properties of MicroGARD 200 were investigated via gavage in guinea pigs using an active systemic anaphylaxis (ASA) challenge [Annals of Allergy 67 (1991) 400; Allergy 49 (1994) 361]. There was no evidence of any anaphylactic sensitizing properties for MicroGARD 200.
Our previous data demonstrated that Ras activation is necessary and sucient for transforming grow... more Our previous data demonstrated that Ras activation is necessary and sucient for transforming growth factor b (TGFb)-mediated Erk1 activation, and is partially required for the inhibition of cyclin-dependent kinase 2 (Cdk2) activity, cyclin A expression and DNA synthesis by TGFb (KM Mulder and SL Morris,
Hydroquinone (HQ) exposure is common as it is a natural component of plant-based foods and is use... more Hydroquinone (HQ) exposure is common as it is a natural component of plant-based foods and is used in some fingernail polishes, hair dyes, and skin lighteners. Industrially it is used as an antioxidant, polymerization inhibitor, and reducing agent. The current study was undertaken to determine whether HQ may cause DNA damage in an in vivo comet assay in F344 rats. DNA strand breaks were assessed in the duodenum as a direct tissue contact site, the testes, and the liver and kidneys, which were tumor sites in bioassays. Rats were exposed to HQ by gavage at 0, 105, 210, or 420 mg/kg/day. At all dose levels, mean % tail intensity and tail moment values for all tissues in animals given HQ were similar to the control. There were no statistically significant increases in tail intensity in any tissue following HQ treatment of male and female rat and data for all animals fell within the available historical control ranges for each tissue. There was no evidence of induction of DNA damage in cells isolated from duodenum, kidney or liver of male and female rats or in the testes of male rats following exposure to HQ at a dose levels up to 420 mg/kg/day, which caused acute renal necrosis.
Our previous data demonstrated that Ras activation is necessary and sucient for transforming grow... more Our previous data demonstrated that Ras activation is necessary and sucient for transforming growth factor b (TGFb)-mediated Erk1 activation, and is partially required for the inhibition of cyclin-dependent kinase 2 (Cdk2) activity, cyclin A expression and DNA synthesis by TGFb (KM Mulder and SL Morris,
We have previously demonstrated that growth inhibition of untransformed intestinal epithelial cel... more We have previously demonstrated that growth inhibition of untransformed intestinal epithelial cells by transforming growth factor  1 (TGF) and TGF 2 was associated with a rapid activation of both Ras and extracellular signal-regulated kinase 1 (Erk1) (Mulder, K.
Fifty percent of human colon carcinomas contain activating mutations in the K-ras gene. However, ... more Fifty percent of human colon carcinomas contain activating mutations in the K-ras gene. However, whether these alterations in K-ras affect the function of Ras proteins in growth factor (GF) signal transduction is now known. Here we have characterized a previously defined human colon carcinoma cell model system for K-ras gene mutations and for altered levels of Ras protein expression and have examined whether these alterations affect Ras function in GF signal transduction. Sequence analysis of PCR-amplified K-ras gene fragments indicated that among the more aggressive cell lines, four had a normal K-ras sequence, whereas 3 others (isolated from the same human tumor) contained a mutation at codon 13. In contrast, all 7 of the less aggressive cell lines contained a mutation at either codon 12 or 13. In addition to the presence of a K-ras mutation, one cell line expressed higher levels of the K-Ras protein and displayed elevated Ras-GTP loading (in the absence of GF addition) compared with the other cell lines examined. Despite these alterations, the mitogenic GF combination epidermal growth factor + insulin + transferrin resulted in an activation of Ras and extracellular signal-regulated kinase 2. Collectively, our results indicate that the malignant phenotype of the cell lines was not correlated with the presence of K-ras mutations or with higher levels of Ras protein expression. Furthermore, K-ras mutations, high levels of K-Ras protein expression, and elevated Ras-GTP loading, as they occur naturally in human colon carcinomas, do not abolish the function of Ras in GF signaling.
Hydroquinone (HQ) exposure is common as it is a natural component of plant-based foods and is use... more Hydroquinone (HQ) exposure is common as it is a natural component of plant-based foods and is used in some fingernail polishes, hair dyes, and skin lighteners. Industrially it is used as an antioxidant, polymerization inhibitor, and reducing agent. The current study was undertaken to determine whether HQ may cause DNA damage in an in vivo comet assay in F344 rats. DNA strand breaks were assessed in the duodenum as a direct tissue contact site, the testes, and the liver and kidneys, which were tumor sites in bioassays. Rats were exposed to HQ by gavage at 0, 105, 210, or 420 mg/kg/day. At all dose levels, mean % tail intensity and tail moment values for all tissues in animals given HQ were similar to the control. There were no statistically significant increases in tail intensity in any tissue following HQ treatment of male and female rat and data for all animals fell within the available historical control ranges for each tissue. There was no evidence of induction of DNA damage in cells isolated from duodenum, kidney or liver of male and female rats or in the testes of male rats following exposure to HQ at a dose levels up to 420 mg/kg/day, which caused acute renal necrosis.
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