Competitive Binding and Metabolism of Several Carcinogenic Polycyclic Aromatic Hydrocarbons by AKR Mouse Embryo Cells in Culture

Thomas H. Zytkovicz, Harold L. Moses, Thomas C. Spelsberg

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The binding of labeled carcinogens [3H]benzo(a)pyrene [3H]dibenz(ah)anthracene, and [3H]dibenz(a,c)anthracene to nuclear chromatin was examined in AKR mouse embryo cells grown in culture. The influence of unlabeled weakly and strongly carcinogenic polycyclic aromatic hydrocarbons (PAH) and the metabolic inhibitor 7,8-benzoflavone on the binding of labeled PAH to nuclear chromatin was examined. Several unlabeled, strongly carcinogenic PAH [benzo(a)pyrene, dibenz(a,h)anthracene, dibenz(a,c)anthracene, and 3-methylcholanthrene] and 7,8-benzoflavone effectively inhibited covalent binding of labeled strongly carcinogenic PAH to the nuclear subfractions. The weakly carcinogenic PAH (pyrene and anthracene) had a variable effect. Since the covalent binding of PAH to chromatin is dependent on the metabolism of the parent compounds, the effects of the various unlabeled PAH on metabolism of the labeled PAH were evaluated. The data indicated: (a) that unlabeled strongly carcinogenic PAH inhibited the metabolism of the labeled carcinogenic PAH, thus causing the decreased nuclear binding of the latter; and (b) that unlabeled weakly carcinogenic PAH stimulated the metabolism and had a variable effect on nuclear binding of the strongly carcinogenic PAH. A reciprocal relationship was seen. With higher levels of inhibition, lower amounts of nuclear binding were seen. The ability of various unlabeled PAH to compete with the metabolism and nuclear binding of labeled carcinogenic PAH appears to relate to the carcinogenic potency of the former compounds. The data suggest the existence of a common metabolic pathway for strongly carcinogenic PAH that differs, at least in part, from that of the weakly carcinogenic PAH.

Original languageEnglish (US)
Pages (from-to)2307-2313
Number of pages7
JournalCancer research
Volume38
Issue number8
StatePublished - Aug 1978

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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