Metabolism of Benzo(A)Pyrene and (-)-Frans-7,8-Dihydroxy-7,8-Dihydrobenzo(A)Pyrene by Rat Liver Nuclei and Microsomes

John M. Pezzuto, Chung S. Yang, Shen K. Yang, David W. McCourt, Harry V. Gelboin

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

The metabolism of benzo(a)pyrene and (-)-frans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene was examined by high-pressure liquid chromatography. Liver nuclei or microsomes from control, 3-methylcholanthrene-treated, or phenobarbital-treated rats were used. An improved method of separating the metabolites is described. Upon treatment with 3-methylcholanthrene, metabolism of benzo(a)pyrene was enhanced 4- and 9-fold in microsomes and nuclei, respectively. No enhancement was observed with phenobarbital treatment. The pattern of metabolites obtained with nuclei was similar to that of the corresponding microsomes, although quantitatively reduced. Nuclei and microsomes also metabolized (-)-frans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene to 7,8-diol-9,10-epoxides and again the metabolic pattern was similar. Each of the nuclear samples produced less diol-epoxides than did the corresponding microsomes. Treatment with 3-methylcholanthrene caused an 8-fold increase in r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol-epoxide I) formation with microsomes but only a 2-fold increase with nuclei. Inducible, r-7,t-8-dihydroxy-c-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol-epox-ide II) formation was also detected. Phenobarbital treatment did not greatly increase diol-epoxide formation. Since both the microsomes and the nuclei can produce diol-epoxides, both organelles may be considered as potentially important sites of carcinogen activation.

Original languageEnglish (US)
Pages (from-to)1241-1245
Number of pages5
JournalCancer Research
Volume38
Issue number5
StatePublished - May 1 1978
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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