Science Inventory

QUANTITATIVE EVALUATION OF PUTATIVE HUMAN CARCINOGENS AND RELATED CHEMICALS ON HUMAN FORESKIN FIBROBLASTS

Citation:

Kurian, P., S. Nesnow, AND G. Milo. QUANTITATIVE EVALUATION OF PUTATIVE HUMAN CARCINOGENS AND RELATED CHEMICALS ON HUMAN FORESKIN FIBROBLASTS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-90/137 (NTIS PB91109751), 1990.

Description:

We have evaluated 12 compounds representative of diverse classes of chemicals for their cytotoxicity and transforming ability of human skin fibroblasts in vitro in the presence and absence of human liver S-9 mix. n the absence of the human liver S-9 mix, only seven of the 12 compounds were highly cytotoxic in the 0-100 ug/ml range and their order of cytotoxicity was: 2,5-bis(1-aziridnyl)-3,6-bis(carboethoxyamino)-1,4-benzoquinone (AZQ) > cis-platin > N, N-aflatoxin B1 (AFB1)> he other five compounds, aflatoxin B2 (AFB2), methylmethacrylate, 1-naphthalamine, 2-naphthylamine, and cyclophosphamide, exhibited less than 40% inhibition of colony formation even at 100 ug/ml of the compound (the maximum concentration of AFB2 used was 50 ug/ml due to its poor solubility). ytotoxicity was not significantly altered in the presence of human liver S-9 mix except for AFB1 and styrene oxide treatment. here was a drastic increase in cytotoxicity following treatment with 1 ug/ml or more AFB1 and a significant reduction in cytotoxicity following treatment with 100 ug/ml styrene oxide in the presence of S-9 mix. nchorage independent growth (AI) of treated cells in soft agar was used as a biological end point for the expression of chemical transformation. FB1 had strong transforming ability while aflatoxin B2 (AFB2) was a weak transforming agent. he transforming abilities of 1-naphthylamine, 2-napthylamine, BCME, cyclophosphamide, acrylonitrile, styrene oxide, cis-platin, AZQ and methylmethacrylate ranged between those of AFB1 and AFB2. hlornaphazaine exhibited a dose dependent increase in AI frequency for at least three consecutive concentrations. hus AI colony forming ability of the carcinogen treated cells may be the best marker, at present, to measure the carcinogenic potential of putative carcinogens.