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DNA ADDUCTS, METABOLISM, AND MORPHOLOGICAL TRANSFORMING ACTIVITY OF ACEANTHRYLENE IN C3H10T1/2CL8 CELLS
Citation:
Nesnow, S., J. Ross, N. Mohapatra, R. Gupta, R. Sangaiah, AND A. Gold. DNA ADDUCTS, METABOLISM, AND MORPHOLOGICAL TRANSFORMING ACTIVITY OF ACEANTHRYLENE IN C3H10T1/2CL8 CELLS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-89/055.
Description:
Aceanthrylene (ACE), a cycioponta-fused polycyclic aromatic hydrocarbon (CP-PAH) related to anthracene, has been studied for Its ability to be metabolized, to form DNA adducts, and to morphologically transform C3H101/2CL8 mouse embryo fibroblasts in culture. lthough ACE has been previously shown to be a strong mutagen in Salmonella typhimurium strains TA89 and TA100, it did not transform C3H101/2 cells (0.4-16 ug/ml) under two treatment protocols: treatment (for 21 hr) 1 day after seeding the cells; treatment (for 24 hr) 5 days after seeding the cells. ath protocols are effective in detecting the morphologlcai transforming activity of PAH and CP-PAH and the latter protocol has been shown to be effective in detecting chemicals which are active in the first protocol only with the additional treatment of the cel is with a tumor promoter. ACE is metabolized by C3H10T1/2 cells to ACE-1,2-dihydrodiol (the cyclopenta-ring dihydrodioll at a rate of 450 pmoles ACE-1,2-dihydrodiol formed/hr/106 cells. ACE-7,8-dihydrodiol and ACE-9,10-dihydrodiol, identified as major Aroclor-1254 induced rat liver microsomal matabolites from their UV, NMR, and mass spectral data, were not identified in incubations of C3H10T1/2 cells with ACE. CE-DNA adducts in C3H10T1/2 cells were isolated, separated, identified, and quantitated using the 37P-postlabeling method. CE forms four major adducts and each was Identified as ACE-1,2-oxide/2-de-oxygunnosine adducts. he level of adductlon was 2.18 pmoles ACE adducts/mg 011A after a 24 hr incubation of ACE (16 ug/ml) with C3HI0T1/2 cells. CE-DNA adduct persistence and repair were evaluated in C3HI0T1/2 cells using a hydroxyurea block after ACE treatment. ACE-DNA adducts were not repaired under the conditions used in the morphological transformation studies. hus, ACE provides an interesting example of a mutagenic PHA which is metabolized by C3H10TI/2 cells to active intermediates, forms relatively stable and persistent 2'-deoxyguanosine adducts in C3HI0TI/2 cells, and yet induces no detectable morphological transforming activity under the experimental conditions used.