Comparison of repair of O6-methylguanine produced by N-methyl-N'-nitro-N-nitrosoguanidine in mouse and human cells

Abstract

The repair of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-produced O ⁶ -methylguanine (O ⁶ -MeG) in DNA and its correlation with MNNG-produced cell-killing and sister chromatid exchange (SCE) induction were compared in mouse and reference human tumor cell strains. As a result, mouse cell strains were divided into three groups: (i) cells proficient in O ⁶ -MeG-repair and insensitive to MNNG similar to human Mer ⁺ Rem ⁺ strains; (ii) cells deficient in O ⁶ -MeG-removal and sensitive to MNNG similar to human Mer ⁻ Rem ⁻ strains; (iii) cells deficient in O ⁶ -MeG-removal but insensitive to MNNG similar to some SV40-transformed human strains. Attempts at correlating lack of capacity for O ⁶ -MeG-removal, MNNG-sensitivity and high SCE induction showed that O ⁶ -MeG in DNA may be a lesion common to cell-killing and SCE induction only in mouse cells of groups i and ii. Levels of O ⁶ -MeG-DNA methyttransferase activity in mouse cells were measured and the enzyme had the same molecular weight as that in human cells.