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

Abstract

Human colon cells (LS174T) were treated with the model colon carcinogen 1,2-dimethylhydrazine (DMH) to determine the production of O(6)-methylguanine DNA adducts. Three known P450 inducers (benzanthracene, pyrazole and phenobarbital) were used to produce different P450 environments in each group of cells prior to treatment with DMH. An increased level of DNA damage of different degrees above uninduced levels was observed in all treated groups. Inhibition of the natural protection systems (glutathione and O(6)-methyltransferase) were also included in the study. Glutathione apparently is not of significant 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 isoforms.