REGULATION OF THE BINDING OF 7,12-DIMETHYLBENZ[A]-ANTHRACENE TO DNA OF CULTURED MURINE EPIDERMAL-CELLS AT METABOLIC LEVEL - COMPETITION OF THE BINDING BY POLYCYCLIC AROMATIC-HYDROCARBONS AND BY OTHER PRE-CARCINOGENS

The binding of labeled carcinogen [3H]DMBA to murine epidermal cells (MEC) DNA in culture has been studied. The influence of unlabeled non-carcinogenic and carcinogenic polycyclic aromatic hydrocarbons (PAH), several PAH metabolites, and various directly and indirectly acting non-PAH carcinogens on the binding of [3H]DMBA to MEC DNA has been examined. All the carcinogenic PAH and some of non-carcinogenic PAH effectively inhibit the binding of [3H]DMBA to MEC DNA. The non-PAH chemical carcinogens requiring metabolic activation also reduce the binding of labeled DMBA to MEC DNA; however, a higher concentration of these compounds is required for 50% inhibition of binding than the concentrations of PAH for the same degree of inhibition of binding of [3H]DMBA to MEC DNA. The directly acting carcinogens do not significantly inhibit the binding of [3H]DMBA to DNA. The relationship between structures of PAH and their ability to inhibit the binding of [3H]DMBA to MEC DNA is also discussed. Thus, it appears that the binding of DMBA to cellular DNA is primarily controlled at a level of metabolism and to some extent at the level of binding of reactive metabolites to DNA. © 1979.