ascorbic-acid and 2-amino-3-methylimidazo(4-5-f)quinoline

The contribution of oxidative stress, different types of DNA damage and expression of DNA repair enzymes in colon and liver mutagenesis induced by 2-amino-3-methylimidazo [4,5-f]quinoline (IQ) was investigated in four groups of six Big Blue rats fed diets with 0, 20, 70, and 200 mg IQ/kg for 3 weeks. There were dose-response relationships of DNA adducts ((32)P-postlabeling) and DNA strand breaks (comet assay) in colon and liver tissues, with the highest levels of DNA adducts and strand breaks in the colon. There was dose-dependent induction of mutations in both the colon and the liver, and the same IQ dose produced two-fold more cII mutations in the liver compared with the colon. The IQ-induced mutation spectrum in the colon was not significantly different to that of control rats. The expression of ERCC1 and OGG1 was higher in the colon than liver, and was unaffected by the IQ diet. Investigations of oxidative stress biomarkers produced inconclusive results. Oxidative DNA damage detected by the endonuclease III enzyme and 7-hydro-8-oxo-2'-deoxyguanosine in colon, liver and/or urine was unaltered by IQ. However, there was increased level of gamma-glutamyl semialdehyde in liver proteins, indicating a higher rate of protein oxidation in the liver following IQ administration. In plasma and erythrocytes there were unaltered levels of oxidized protein, malondialdehyde, and antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, catalase, glutathione reductase) indicating no systemic oxidative stress. However, the level of total vitamin C was increased in plasma, with the largest fraction being in the reduced form. In conclusion, our results indicate that DNA adducts rather than oxidative stress are responsible for the initiation of IQ-induced carcinogenesis of the liver and colon. A lower frequency of mutations in the colon than in the liver could be related to higher expression of DNA repair enzymes in the former.

Topics: Animals; Ascorbic Acid; Base Sequence; Colon; DNA Damage; DNA Primers; DNA Repair; Liver; Mutagens; Oxidative Stress; Polymerase Chain Reaction; Quinolines; Rats; Rats, Mutant Strains

Our aim was to determine the antimutagenic activity of various solvent extracts from an herb Mesona procumbens Hemsl, normally called Hsian-tsao in China. We also investigated the relationships between the special components in the water extract of Hsian-tsao (WEHT) and the antimutagenic activity. It was found that the extracts at 0-0.6 mg/plate from three solvents (water, methanol, and ethyl acetate) exhibited a dose-dependent antimutagenic effect against benzo[a]pyrene [B(a)P] and 2-amino-3-methylimidazo(4,5-f)quinoline (IQ), both are indirect mutagens in Salmonella tester strains TA98 and TA100. The WEHT from three different plantations revealed a similar inhibitory effect on the mutagenicity of IQ in TA 98 at 2.5-5.0 mg/plate. The inhibitory effect of WEHT on the mutagenicity of IQ correlates with their polyphenol and ascorbic acid contents but not with their chlorophyll contents. These findings suggest that the antimutagenicity activity of WEHT may be attributed mainly to their polyphenolic compounds and ascorbic acid.

Topics: Acetates; Antimutagenic Agents; Ascorbic Acid; Benzo(a)pyrene; Chlorophyll; Flavonoids; Medicine, Chinese Traditional; Methanol; Mutagenicity Tests; Mutagens; Phenols; Plant Extracts; Plants, Medicinal; Polymers; Polyphenols; Quinolines; Solvents; Water