Anticarcinogenic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene tumor initiation and its relationship to DNA binding

Journal Article · Mon Oct 01 04:00:00 EDT 1979 · Cancer Res.; (United States)

OSTI ID:6807234

Cohen, G M; Bracken, W M; Iyer, R P; Berry, D L; Selkirk, J K; Slaga, T J

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) pretreatment inhibits the carcinogenicity of both benzo(a)pyrene (B(a)P) and dimethylbenz(a)anthracene when they are applied as skin tumor initiators in female Sencar mice. TCDD caused a marked decrease in the in vivo covalent binding of dimethylbenz(a)anthracene to DNA and RNA but caused a significant increase in the in vivo binding of B(a)P to DNA with relatively little change in RNA binding. The in vivo binding of B(a)P to DNA in the absence of TCDD pretreatment was accompanied by formation of a major hydrocarbon-deoxyribonucleoside adduct which cochromatographed with 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene bound to the exocyclic amino group of guanine. The increased in vivo binding to DNA following pretreatment with TCDD did not results in the formation of detectable amounts of this adduct but in the formation of other, as yet unidentified, adducts. It is suggested, partly on our observation, that the absence of the adduct of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene bound to guanine corresponded to the marked tumor-inhibitory properties of TCDD and that formation of this adduct may be a critical but by itself an inadequate step in B(a)P-induced mouse skin carcinogenesis. Thus, the inhibition by TCDD of B(a)P skin tumorigenesis correlated with the loss of known hydrocarbon-deoxyribonucleoside adducts but not with the total binding to DNA. This stresses the importance of the qualitative, not just the quantitative, nature of the hydrocarbon-DNA interactions and its subsequent relationship to carcinogenesis.

• Research Organization: Oak Ridge National Lab., TN
• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 6807234
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 39; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTINEOPLASTIC DRUGS
AROMATICS
BENZOPYRENE
BIOLOGICAL EFFECTS
CARCINOGENESIS
CONDENSED AROMATICS
DIMETHYLBENZANTHRACENE
DISEASES
DNA
DRUGS
HYDROCARBONS
INHIBITION
MAMMALS
MICE
MOLECULAR BIOLOGY
NEOPLASMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PATHOGENESIS
RNA
RODENTS
TOXICITY
VERTEBRATES