||Ohio State Univ., Columbus. Dept. of Physiological Chemistry.;Health Effects Research Lab., Research Triangle Park, NC.;Air Force Office of Scientific Research, Bolling AFB, DC.;National Cancer Inst., Bethesda, MD.
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 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.