title: Correlation between specific DNA-methylation products and mutation induction at the HGPRT locus in Chinese hamster ovary cells.
abstract: Suspension cultures of Chinese hamster ovary (CHO) cells were exposed to methyl methanesulfonate (MMS) or methylnitrosourea (MNU) and assayed for mutation induction (6-thioguanine resistance) and for specific DNA adducts. DNA methylation at the 1-, 3- and 7-positions of adenine, the 3-, O6- and 7-positions of guanine, and phosphate was detected in cultures exposed to MMS, while MNU produced 3- and 7-methyladenine, 3-methylcytosine, 3-, O6- and 7-methylguanine, O4-methylthymidine and methylated phosphodiesters. When mutations induced by MMS and MNU were compared by linear correlation analysis with levels of each of these adducts, only O6-methylguanine displayed a strong correlation with mutations (r = 0.879, p less than 0.001). The relationship between O6-methylguanine and induced mutations in CHO cells is similar to that previously reported in CHO cells for O6-ethylguanine and mutations (Heflich et al., 1982) and indicates that alkylation-induced mutations at the HGPRT locus in CHO cells are primarily associated with O6-alkylguanine formation.
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000378:metabolism*; D005260:Female; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008741:Methyl Methanesulfonate / Q000494:pharmacology*; D008745:Methylation; D008770:Methylnitrosourea / Q000494:pharmacology*; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D010053:Ovary / Q000187:drug effects / Q000378:metabolism
chemical_list: D009607:Nitrosourea Compounds; D008770:Methylnitrosourea; D004247:DNA; D008741:Methyl Methanesulfonate; D007041:Hypoxanthine Phosphoribosyltransferase