Oxidant-dependent metabolic activation of polycyclic aromatic hydrocarbons by phorbol ester-stimulated human polymorphonuclear leukocytes: possible link between inflammation and cancer
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), Vol. 82:15
- Country of Publication:
- United States
- Language:
- English
Similar Records
Carcinogenicity of benzo(a)pyrene and thirteen of its derivatives in C3H/fCum mice
Promotion of DNA strand breaks in cocultured mononuclear leukocytes by protein kinase C-dependent prooxidative interactions of benoxaprofen, human polymorphonuclear leukocytes, and ultraviolet radiation
Related Subjects
LEUKOCYTES
CHEMICAL ACTIVATION
PHORBOL ESTERS
BIOLOGICAL EFFECTS
POLYCYCLIC AROMATIC HYDROCARBONS
METABOLIC ACTIVATION
CARCINOGENESIS
CHEMILUMINESCENCE
DNA
INFLAMMATION
MAN
MUTAGENESIS
SALMONELLA TYPHIMURIUM
ANIMALS
AROMATICS
BACTERIA
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARCINOGENS
ESTERS
HYDROCARBONS
LUMINESCENCE
MAMMALS
MATERIALS
MICROORGANISMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PATHOGENESIS
PATHOLOGICAL CHANGES
PRIMATES
SALMONELLA
SYMPTOMS
VERTEBRATES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)