Relationships between specific DNA adducts, mutation, cell survival, and SCE formation. 1984

S M Morris, and R H Heflich, and D T Beranek, and F A Beland

The induction of biological responses and the formation of specific DNA adducts by 2 classes of carcinogens have been compared in CHO cells. The simple alkylating agents reacted with a variety of nucleophilic centers within DNA while the N-oxidized arylamines reacted only at C8 of deoxyguanosine. With the alkylating agents, mutation induction, which correlated strongly with 0(6)-alkylguanine levels, did not correlate well with either SCE frequency or cell survival. SCE formation correlated strongly with reduced cell survival but could not be related to the concentration of a single DNA adduct. Exposure of CHO cells to each of the 3 N-oxidized arylamines resulted in a single DNA adduct, substituted through the C8 of deoxyguanosine. When arylamine-induced biological responses were compared, the results were similar to those found with the alkylating agents. That is, mutation induction did not relate well with either SCE frequency or cell survival, although a close relationship was found between the latter 2 responses. These results suggest that both the site of substitution and the DNA adduct structure may be important in eliciting genotoxic responses. These results also suggest that the toxic and SCE-inducing effects of these 2 classes of carcinogens may be related.

UI MeSH Term Description Entries
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D010053 Ovary The reproductive organ (GONADS) in female animals. In vertebrates, the ovary contains two functional parts: the OVARIAN FOLLICLE for the production of female germ cells (OOGENESIS); and the endocrine cells (GRANULOSA CELLS; THECA CELLS; and LUTEAL CELLS) for the production of ESTROGENS and PROGESTERONE. Ovaries
D011721 Pyrenes A group of condensed ring hydrocarbons.
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D003412 Cricetulus A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research. Hamsters, Armenian,Hamsters, Chinese,Hamsters, Grey,Armenian Hamster,Armenian Hamsters,Chinese Hamster,Chinese Hamsters,Grey Hamster,Grey Hamsters,Hamster, Armenian,Hamster, Chinese,Hamster, Grey
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D005260 Female Females
D005449 Fluorenes A family of diphenylenemethane derivatives.

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