Relationship between cell killing, chromosomal aberrations, sister-chromatid exchanges and point mutations induced by monofunctional alkylating agents in Chinese hamster cells. A correlation with different ethylation products in DNA.
Several monofunctional alkylating agents (AA) were compared for their ability to induce chromosomal aberrations, cell killing, sister-chromatid exchanges (SCE) and point mutations in Chinese hamster cells (CHO and V79 cells). The AAs chosen varied in their reaction kinetics as well as their affinity to nucleophilic sites (different s values). AAs with low s values were more mutagenic in comparison to those with high s values, whereas the reverse was true for induction of cytotoxic effects. Neither SCEs nor chromosomal aberrations correlated with the induction of point mutations, indicating that different primary DNA lesions and repair pathways are involved in these biological processes. Molecular dosimetric studies indicate that O6 alkylation of guanine is the most probable cause of lesions in DNA leading to point mutations following treatment with ethyl methanesulphonate and ethyl nitrosourea.
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D006224:Cricetinae; D003434:Crossing Over, Genetic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005020:Ethyl Methanesulfonate / Q000633:toxicity; D005038:Ethylnitrosourea / Q000633:toxicity; D005260:Female; D008741:Methyl Methanesulfonate / Q000633:toxicity; D008770:Methylnitrosourea / Q000633:toxicity; D009154:Mutation / Q000187:drug effects*; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013463:Sulfuric Acid Esters / Q000633:toxicity
D000477:Alkylating Agents; D013463:Sulfuric Acid Esters; D008770:Methylnitrosourea; D005020:Ethyl Methanesulfonate; D008741:Methyl Methanesulfonate; C007482:dimethyl sulfate; D005038:Ethylnitrosourea