Role of cytochrome P450 in DNA damage produced by treatment of colon cellswith 1,2-dimethylhydrazine

Human colon cells (LS174T) were treated with the model colon carcinogen 1,2 -dimethylhydrazine (DMH) to determine the production of O-6-methylguanine D NA adducts. Three known P450 inducers (benzanthracene, pyrazole and phenoba rbital) were used to produce different P450 environments in each group of c ells prior to treatment with DMH. An increased level of DNA damage of diffe rent degrees above uninduced levels was observed in all treated groups. Inh ibition of the natural protection systems (glutathione and O-6-methyltransf erase) were also included in the study. Glutathione apparently is not of si gnificant protection against DMH damage in colon cells challenged with DMH. In contrast methyltransferase does exert a protective role in this type of cells by reducing the extent of DNA O-6-methylguanine adduct formation in colon cells following induction of different panels of cytochrome P450 isof orms.