Chinese hamster cells harbouring the Escherichia coli O6-alkylguanine alkyltransferase gene are less susceptible to sister chromatid exchange induction and chromosome damage by methylating agents.
Clones of Chinese hamster V79 cells harbouring the Escherichia coli O6-alkylguanine (O6-AG) alkylphosphotriester (AP) alkyltransferase (ATase) gene (clone 8) or a subclone of it that codes only for O6-AG ATase activity (clone SB) have been exposed to increasing doses of N-methyl-N-nitrosourea (MNU) or methylmethanesulphonate (MMS) and the frequencies of induced sister chromatid exchanges (SCEs) measured. In control (clone 2) cells, SCE induction was almost linearly proportional to dose of MNU or MMS and at the highest doses used (15 or 80 micrograms/ml) SCE frequencies were 6 or 8 times background levels, respectively. Slightly lower levels of MMS-induced SCEs were seen in clone 8 and clone SB cells whilst, in contrast, MNU-induced SCE levels in these two clones were drastically reduced being less than twice background levels at 15 micrograms/ml. After treatment with N-butyl-N-nitrosourea, SCE frequency was similar in all three clones. At higher doses, MNU treatment produced less chromatid aberrations and micronuclei in clone SB than in clone 2 cells. These results suggest that ATase-repairable damage is involved in the induction of SCE, chromosome aberrations and micronuclei in V79 cells.
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004926:Escherichia coli / Q000235:genetics; D006147:Guanine / Q000031:analogs & derivatives / Q000633:toxicity; D008741:Methyl Methanesulfonate / Q000633:toxicity; D008770:Methylnitrosourea / Q000633:toxicity; D008780:Methyltransferases / Q000235:genetics*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D012854:Sister Chromatid Exchange
D000477:Alkylating Agents; D006147:Guanine; D008770:Methylnitrosourea; C008449:O-(6)-methylguanine; D008741:Methyl Methanesulfonate; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase