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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Autrup, H. Articles by Jeffrey, A. M. Search for Related Content PubMed PubMed Citation Articles by Autrup, H. Articles by Jeffrey, A. M.

Metabolism of Benzo(a)pyrene and Identification of the Major Benzo(a)pyrene-DNA Adducts in Cultured Human Colon¹

Human Tissue Studies Section, Laboratory of Experimental Pathology, Carcinogenesis Research Program, National Cancer Institute, Bethesda, Maryland 20014 [H. A., C. C. H.]; Department of Pathology, University of Maryland, School of Medicine, Baltimore, Maryland 21201 [B. F. T.]; and Institute of Cancer Research, Columbia University, College of Physicians and Surgeons, New York, New York 10032 [A. M. J.]

The metabolism of benzo(a)pyrene in cultured human colon has been investigated. Nontumorous colonic tissue was collected at the time of either surgery or "immediate autopsy" from patients with or without colonic cancer. After 24 hr in culture the explants were exposed to [³H]benzo(a)pyrene for another 24 hr and the binding to cellular DNA and protein was measured. Two adducts, formed between benzo(a)pyrene and DNA, have been isolated. The major adduct (72 to 100%) was formed between the 10-position of benzo(a)pyrene diol-epoxide I and the 2-amino group of guanine, and the minor adduct was formed between benzo(a)pyrene diol-epoxide II and the 2-amino group of guanine. The major metabolites of benzo(a)pyrene extracted with ethyl acetate/acetone from the tissue culture media were (7,10/8,9)-tetrahydroxy-7,10,8,9-tetrahydrobenzo(a)pyrene, trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene, and a peak containing (7,9,10/8)-tetrahydroxy-7,10,8-9-tetrahydrobenzo(a)pyrene, (7/8,9)-trihydroxy-7,8-dihydrobenzo(a)pyrene, and trans-9,10,dihydroxy-9,10-dihydrobenzo(a)pyrene. The relative distribution of benzo(a)pyrene metabolites formed by cultured colon varied among individuals. About 10% of the metabolites remained in the water phase after extraction with ethylacetate/acetone. trans-7,8-Dihydroxy-7,8-dihydrobenzo(a)pyrene and quinones were the major metabolites released when the water-soluble metabolites were treated with ß-glucuronidase and arylsulfatase. The binding levels of benzo(a)pyrene to DNA in cultured colon showed a unimodal distribution (56 cases). A slight difference (p < 0.1) in binding levels between nontumorous tissues from cancer patients (40 cases) and tissues from noncancer patients (16 cases) was observed, the binding level being highest in the latter. The binding level of benzo(a)pyrene to DNA also showed approximately a 5-fold variation among the different anatomical segments of the colon from the same patient; the binding level was generally highest in the ascending colon. Coincubation of the explants with benzo(a)pyrene and either taurodeoxycholic acid or lithocholic acid increased the binding levels of benzo(a)pyrene to DNA. An increased level of trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene in the culture media was also observed when explants were coincubated with either taurodeoxycholic acid or lithocholic acid.

These results indicate that cultured human colon can metabolize benzo(a)pyrene by pathways similar to those found in human bronchus and in cells of experimental animals.

¹ This work was supported in part by NIH Contract N-01-CP 43237 and by NIH Grant CA 21111-01.

² To whom requests for reprints should be addressed, at Building 37, Room 3A09, NIH, Bethesda, Md. 20014.

Received 5/12/78. Accepted 8/ 2/78.

This article has been cited by other articles:

				S. A. Leavitt, M. H. George, T. Moore, and J. A. Ross Mutations induced by benzo[a]pyrene and dibenzo[a,l]pyrene in lacI transgenic B6C3F1 mouse lung result from stable DNA adducts Mutagenesis, June 23, 2008; (2008) gen033v1. [Abstract] [Full Text] [PDF]