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Oxidant-dependent metabolic activation of polycyclic aromatic hydrocarbons by phorbol ester-stimulated human polymorphonuclear leukocytes: possible link between inflammation and cancer

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
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Oxidants, such as those generated by metabolically activated phagocytes in inflammation, have been implicated in the metabolic activation of carcinogens, and in this study the authors demonstrate that the interaction of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (BP 7,8-dihydrodiol) with phorbol ester-stimulated polymorphonuclear leukocytes (PMNs) results in the generation of both a chemiluminescent intermediate and one that covalently binds to DNA. Concordant with the formation of a carcinogen-DNA adduct, the admixture of BP 7,8-dihydrodiol and phorbol ester-stimulated PMNs elicited mutagenesis in Salmonella typhimurium strain TA100. These results demonstrate that oxidants generated by metabolically stimulated PMNs can activate penultimate polycyclic aromatic hydrocarbons to a genotoxic metabolite and further defines a role for inflammation in carcinogenesis.

Research Organization:
Johns Hopkins School of Hygiene and Public Health, Baltimore, MD
OSTI ID:
6081059
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 82:15; ISSN PNASA
Country of Publication:
United States
Language:
English

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Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AROMATICS
BACTERIA
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARCINOGENESIS
CARCINOGENS
CHEMICAL ACTIVATION
CHEMILUMINESCENCE
DNA
ESTERS
HYDROCARBONS
INFLAMMATION
LEUKOCYTES
LUMINESCENCE
MAMMALS
MAN
MATERIALS
METABOLIC ACTIVATION
MICROORGANISMS
MUTAGENESIS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PATHOGENESIS
PATHOLOGICAL CHANGES
PHORBOL ESTERS
POLYCYCLIC AROMATIC HYDROCARBONS
PRIMATES
SALMONELLA
SALMONELLA TYPHIMURIUM
SYMPTOMS
VERTEBRATES