@article{cca82414149f40caa8a39081319240bb,
title = "The importance of the {"}bay region{"} diol-epoxide in 7,12-dimethylbenz[a]anthracene skin tumor initiation and mutagenesis",
abstract = "The skin tumor-initiating and V79 mutagenic activities of various derivatives of 7,12-dimethylbenz[a]anthracene (DMBA) were investigated to determine what possible cellular metabolite(s) may be responsible for its carcinogenicity and/or mutagenicity. 1-,2-,3-,4- and 5-hydroxyDMBA were found to be essentially inactive as skin tumor initiatrs whereas 9- and 10-hydroxy DAMBA had weak activity. The (±)-trans DMBA 8,9- and 5,6-dihydrodiols were also essentially inactive as skin tumor initiators and (±)-DMBA 8β,9α-diol-10α,11α-epoxide had weak skin tumor initiating activity. All of the above tested derivatives of DMBA were essentially inactive as mutagens in the cell-mediated or direct V79 mutagenesis systems. A methyl or fluoro addition to the 1, 2 or 5 positions almost completely blocked the skin tumor initiating and V79 mutagenic activities of DMBA, whereas a fluoro addition to position 11 did not. From our data we suggest that a 'bay region' diol-epoxide may be important in DMBA carcinogenicity and mutagenicity.",
author = "Slaga, {T. J.} and E. Huberman and J. DiGiovanni and G. Gleason and Harvey, {R. G.}",
note = "Funding Information: The skin tumor-initiating and V79 mutagenic activities of various deriw'~tives of 7,12-dimethylbenz\[a\]anthracene (DMBA) were investigated to determine what possible cellular metabolite(s) may be responsible for its carcinogenivity and/or mutagenict~y. 1-,2-,3.,4-and 5-hydroxyDMBA were found to be essentially inactive as skin tumor initiators whereas 9-and 10-hydroxyDMBA had weak activity. The (±)-trans DMBA 8,9-and 5,6-dihydrodiols were also *Research sponsored jointly by the NIH under Interagcney Agreement Grant CA-20076 and by the U.S. Department of Energy, under contract W-7405-eng-26 with the Union Carbide Corporation. **After our manuscript was submitted for publication, Maleveille and coworkers reported the high mutagenie activity of the 3,4-dihydrodiol of DMBA in S. typhimurium TA100 in the presence of a rat liver metabolizing system which agrees with the data presented here. See, Malaveflle, C. Bartseh, H., Tierney, B., Grovar, P.L. and Sims, P. (1978). Miarosome~ mediated mutagenicities of the dihydrodio\]s of 7,12.dirnethyihenz\[a\]anthraeene: High mutagenic activity of the 3,4-dihydrodiol. Bioehem. Biophys. Res. Commun., 83, 1468--1473. t To whom requests for reprints and correspondence shound be addrea~ed to: Biology Division, Oak Ridge National Laboratory, Post Office Box Y, Oak Ridge, Tennessee 37830, U.S.A. T1{"}Present add~.e~: McPadie Laboratory for Cancer Reseaxeh, University of Wisconsin Medical SchooL, Madison, Wisconsin, U.S.A. Abbreviations: BP, benzo\[a\]pyrene;D MBA, 7,12-dimethylbenz\[a\]anthracene;P AH, polycyclic aromatic hydrocarbons; 1-. 2-, 3-, 4-, 5-, 9-and 10-OH DMBA, various phenols of DMBA; DMBA 5,6-diol, (±)trans-5,6-dihydroxy~5,6-d~hydro.DMBA; DMBA 8,9-diol, (±)traas-8,9-dihydroxy-8,9-dihydro-DMBA; DMBA 8,9-diol-.~.0,11-epoxlde, (±)trans-8~, 9~-dihydroxy-I0~,11~-epoxy-8,9,10,11-tetrahydro-DMBA; 1-CH~-, 2-CH3-, 2-CH~, and 5-CH3-DMBA, either 1-, 2 or 5,7,12-trimethylbenz\[a \]anthracene~ 1-, 2-, 5-, and 11-fl-DMBA, 1-, 2-, 5-and 11-flaoro-DMBA; TPA, 12-O-tetradecanoyi-phorbr~l-13-acetate.",
year = "1979",
month = apr,
doi = "10.1016/S0304-3835(79)80036-1",
language = "English (US)",
volume = "6",
pages = "213--220",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
number = "4-5",
}