Characteristics of benzo[a]pyrene and A-ring reduced 7,12-dimethyl benz[a]anthracene induced neoplastic transformation of human cells in vitro.

The polynuclear aromatic hydrocarbons (PAH) benzo[a]pyrene (BP) and the A-ring reduced analogue of 7,12-dimethylbenz[a]anthracene (DMBA), 1,2,3,4-tetrahydro-7,12-dimethylbenz[a]anthracene (TH-DMBA) are carcinogenic to human cells. The unsaturated PAH, DMBA exhibits no carcinogenic activity on human cells as measured by growth in soft agar. The TH-DMBA and BP treated cells exhibit a colony frequency in soft agar of 84 and 86, respectively. These anchorage independent cells, when seeded on the chick embryonic skin (CES) organ cultures, are invasive and form a fibrosarcoma. It is highly unlikely that TH-DMBA, which does not contain an aromatic A-ring, can undergo metabolism in human cells in culture to form a bay region 3,4-dihydrodiol-1,2-epoxide. These results suggest that an alternate mechanism for the induction of carcinogenesis is appropriate to explain the absence of bay region diol-epoxide metabolite as the ultimate form of the carcinogen in TH-DMBA induced carcinogenesis in human diploid cells.