Effect of various chemicals on the metabolism of benzo(a)pyrene by cultured rat colon

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  • Herman Autrup, Human Tissue Studies Section, Experimental Pathology Branch, Division of Cancer Cause and Prevention, NCI, National Institutes of Health, Public Health Service, U.S. Department of Health, Education, and Welfare, Bethesda, Maryland, Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, Denmark
  • Curtis C. Harris, United States
  • Steven Fugaro, United States
  • James K. Selkirk, United States
  • Institute of Environmental and Occupational Medicine
The effect of various co- and anti-carcinogens of colon carcinogenesis on the metabolism of benzo(a)pyrene (BP) in cultured rat colon is reported. Rat colon enzymatically converted BP into metabolites which bind to cellular macromolecules i.e., DNA and protein. Activity of aryl hydrocarbon hydroxylase (AHH) activity and binding levels of BP to macromolecules were higher in the descending colon when compared to other segments. The major metabolites of BP, extractable with ethylacetate, were quinones, tetrols, 7,8-diol and a peak containing 9,10-dihydroxy-9,10-dihydrobenzo(a)pyrene and 7,8,9-trihydroxy-7,8-dihydrobenzo(a)pyrene. The binding levels of BP to DNA and protein in the explant was lowered by co-incubation with 7,8-benzoflavone (7,8-BF) (3.6 and 18.0 micron), a known inhibitor of AHH, and with disulfiram (100 micron), an anti-oxidant. The absence of vitamin A in the media also resulted in a lower level of BP binding to DNA and protein and in lower activity of AHH. Pretreatment with known inducers of AHH such as phenobarbital (PB) or benz(a)anthracene (BA), did not have any significant effect on the binding levels of BP to DNA or on the AHH activity. Of the bile acids investigated only taurodeoxycholic acid significantly increased the binding level of BP to DNA.
Original languageEnglish
JournalChemico-Biological Interactions
Pages (from-to)337-347
Number of pages11
Publication statusPublished - Sep 1977

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