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Title: 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

Abstract

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 bindingmore » 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.« less

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Oak Ridge National Lab., TN
OSTI Identifier:
6807234
Alternate Identifier(s):
OSTI ID: 6807234
DOE Contract Number:  
W-7405-ENG-26
Resource Type:
Journal Article
Journal Name:
Cancer Res.; (United States)
Additional Journal Information:
Journal Volume: 39
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; ANTINEOPLASTIC DRUGS; BIOLOGICAL EFFECTS; BENZOPYRENE; CARCINOGENESIS; DIMETHYLBENZANTHRACENE; DNA; INHIBITION; MICE; MOLECULAR BIOLOGY; NEOPLASMS; RNA; TOXICITY; ANIMALS; AROMATICS; CONDENSED AROMATICS; DISEASES; DRUGS; HYDROCARBONS; MAMMALS; NUCLEIC ACIDS; ORGANIC COMPOUNDS; PATHOGENESIS; RODENTS; VERTEBRATES 560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)

Citation Formats

Cohen, G.M., Bracken, W.M., Iyer, R.P., Berry, D.L., Selkirk, J.K., and Slaga, T.J. 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. United States: N. p., 1979. Web.
Cohen, G.M., Bracken, W.M., Iyer, R.P., Berry, D.L., Selkirk, J.K., & Slaga, T.J. 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. United States.
Cohen, G.M., Bracken, W.M., Iyer, R.P., Berry, D.L., Selkirk, J.K., and Slaga, T.J. Mon . "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". United States.
@article{osti_6807234,
title = {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},
author = {Cohen, G.M. and Bracken, W.M. and Iyer, R.P. and Berry, D.L. and Selkirk, J.K. and Slaga, T.J.},
abstractNote = {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.},
doi = {},
journal = {Cancer Res.; (United States)},
number = ,
volume = 39,
place = {United States},
year = {1979},
month = {10}
}