This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gehly, E. B. Articles by Heidelberger, C. Search for Related Content PubMed PubMed Citation Articles by Gehly, E. B. Articles by Heidelberger, C.

Metabolic Activation of Benzo(a)pyrene by Transformable and Nontransformable C3H Mouse Fibroblasts in Culture¹

Cancer Research Laboratory, University of Southern California, Comprehensive Cancer Center, Los Angeles, California 90033

Incubation of 2.5 µM benzo(a)pyrene (BaP) with C3H/10T or CVP3SC6 (CVP) mouse fibroblasts for 48 hr resulted in the metabolism of 36 to 42% of the BaP to organic soluble derivatives, which cochromatographed with 7,8-trans-dihydroxy-7,8-dihydrobenzo(a)pyrene, 9,10-trans-dihydroxy-9,10-dihydrobenzo(a)-pyrene, 3-hydroxybenzo(a)pyrene, and 9-hydroxybenzo(a)pyrene, or to water-soluble derivatives. The formation of both organic and water-soluble metabolites during the 48-hr period increased proportionally with time, except in the case of BaP phenols, which increased initially but then remained the same or decreased. The distribution of organic soluble metabolites in the extracellular culture medium consisted primarily of BaP diols and was significantly different from that found inside the cells. The intracellular profile of organic soluble metabolites produced by both cell lines consisted predominantly of BaP phenolic derivatives and was qualitatively similar to the spectrum of metabolites produced by the incubation of BaP with C3H/10T or CVP cell microsomes.

The nature of the BaP water-soluble derivatives produced by the C3H/10T and CVP cell lines was investigated by hydrolysis of culture medium with ß-glucuronidase and arylsulfatase. Although sulfation was not a major conjugation pathway for BaP in these cells, glucuronidation of BaP phenols was found to account for 30% of the total water-soluble derivatives.

The similarity in the kinetics and qualitative nature of the metabolism of BaP by C3H/10T and CVP cells indicates that both cell lines are equally capable of biosynthesizing the proximal carcinogen, 7,8-trans-dihydroxy-7,8-dihydrobenzo(a)pyrene. Analysis of the water-soluble metabolites produced by these cells suggests further that the nonresponsiveness of the CVP cells to BaP-induced transformation cannot be accounted for on the basis of an increased detoxication of 7,8-trans-dihydroxy-7,8-dihydrobenzo(a)pyrene.

¹ This work was supported in part by Contract NO1-CP-65831 from the National Cancer Institute, NIH.

² To whom requests for reprints should be addressed.

Received 7/ 6/81. Accepted 3/12/82.