Mutagens in Cooked Foods-Metabolism and Genetic Toxicity
Recently developed in our laboratories is an efficient extraction procedure incorporating XAD resin adsorption which yields from 200°C grilled ground beef an extract containing 230 SalmonellaTA1538 revertants per g fresh weight of original ground beef. These mutagenic components are specific for frameshift-sensitive Salmonellastrains and have an absolute requirement for metabolic activation. S9 activation by cytochrome P-448 inducers, Aroclor 1254 (PCB), 3-methylcholanthrene (3-MC) and B-naphthoflavone(BNF1), resulted in the largest mutagenic response. Phenobarbital induction gave 20% of the PCB response and Pregnenolone-16a-carbonitrile and corn oil were inactive. Human liver microsomes and BNF-induced rodent intestinal S9 were also active metabolizing fractions. Normal-phase HPLC separation of methanol-extractable metabolites generated from reaction of 2-amino-3-methylimidazo [4,5-f] quinoline (IQ), a mutagenic component of broiled food, rat liver microsomes and cofactors resulted in one direct-acting mutagenic peak and a second more polar peak still requiring metabolic activation. Two potent thermally-produced bacterial mutagens, Trp-P-2 and IQ, were examined in mammalian cells. In excision repair-deficient CHO cells, Trp-P-2 exposure caused cytotoxicity, mutagenicity (thioguanine and azaadenine resistances), sister chromatid exchange, and chromosomal aberrations at concentrations more than 30-fold lower than those for IQ. In normal repair-proficient CHO cells Trp-P-2 was one-half as active and IQ was inactive. Relative to Trp-P-2, IQ is much more potent in the Salmonellabacterial system than in mammalian CHO cells.
KeywordsBasic Fraction Ground Beef Genetic Toxicity Mutagenic Component Mutagenic Intermediate
Unable to display preview. Download preview PDF.
- Felton, J.S. Nebert, D.W., and Thorgiersson, S.S. (1976). Genetic differences in 2-acetylaminofluorene mutagenicity in vitro associated with mouse hepatic aryl hyrocarbon hydroxylase activity induced by polycyclic aromatic compounds. Mol. Pharmacol. 12, 225–233.Google Scholar
- Felton, J.S., Healy, S.K., Knize, M., Stuermer, D.H., Berry, P.W., Timourian, HJ., Hatch, F.T., Morris, M., and Bjeldanes, L.F. (1981b) In vitro human and rodent metabolism of mutagenic fractions from cooked ground beef. Environmental Mutagenesis 3, 342.Google Scholar
- Skopek, T.R., Liber, H.L., Kaden, D.A., Thilly, W.G. (1978). Relative sensitivities of forward and reverse mutation assays in Salmonella typhimurium. Proc. Natl. Acad. Sci. USA 75, 4467–4469.Google Scholar