The metabolism of 7,12‐dimethylbenz(A)anthracene in cell cultures

When tritiated 7,12‐dimethylbenz (a)anthracene (DMBA) was incubated in the presence of monolayer cultures of normal embryonic rodent cells, a large fraction of the carcinogen was metabolized to water‐soluble derivatives that could be recovered from the medium. Small amounts of material with chromatographic properties similar to those of the monohydroxymethyl derivatives of DMBA also were recovered from the medium, but no compound resembling the dihydroxymethyl derivative was detected. In the presence of a transformed line of hamster embryo cells and a strain of human diploid cells, DMBA was metabolized to the hydroxymethyl and water‐soluble derivatives to a much lesser extent. The amount of carcinogen metabolized by HeLa cells was intermediate between those of the normal and of the transformed rodent cells, but the main water‐soluble derivatives produced in the presence of rodent cells and HeLa cells were different. Thus, DMBA was metabolized to water‐soluble derivatives primarily by those cells which are sensitive to cytotoxicity induced by the carcinogen, i.e., the normal rodent cells and HeLa cells; the transformed hamster cells and the normal human cells are relatively resistant to the carcinogen‐induced cytotoxicity. The conversion of DMBA to water‐soluble metabolites was inhibited by actinomycin D.