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Title: Mutagenicity and tumor-initiating activity of fluorinated derivatives of 7,12-dimethylbenz(a)anthracene

Abstract

7,12-Dimethylbenz(a)anthracene (DMBA) and its 1-, 2-, 5-, and 11-fluoro derivatives were tested to determine their mutagenicity for ouabain resistance in Chinese hamster V79 cells and their tumor-initiating activity in mouse skin. Inasmuch as V79 cells do not metabolize polycyclic aromatic hydrocarbons, mutagenesis was tested both in the presence and in the absence of golden hamster embryo cells capable of metabolizing polycyclic aromatic hydrocarbons. Neither DMBA nor any of the fluorinated derivatives showed mutagenicity for V79 cells in the absence of the golden hamster cells. In the presence of these cells, DMBA and 11-fluoro-DMBA exhibited a comparable mutagenic response that was dose dependent. At a dose as low as 0.01 ..mu..m, a 7- to 10-fold increase in the frequency of ouabain-resistant mutants was observed. The other derivatives were either inactive or required more than a 1000-fold higher dose to induce a comparable mutagenic response. Similarly, both DMBA and 11-fluoro-DMBA at 100 nmol initiated tumors in 100% of the tested mice, whereas the other fluorinated derivatives at this dose initiated skin tumors in 15% or less of the treated mice. The average number of papillomas per mouse induced by 1-, 2-, and 5-fluoro-DMBA was more than 100-fold lower than the number inducedmore » by DMBA or 11-fluoro-DMBA. These results suggest that carbon positions 1 and 2 of DMBA, which are located at the bay region, and position 5, which is located at the K-region, are involved in the metabolic activation of DMBA into mutagenic and carcinogenic metabolites.« less

Authors:
;
Publication Date:
Research Org.:
Oak Ridge National Lab., TN
OSTI Identifier:
5059493
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.; 59 BASIC BIOLOGICAL SCIENCES; CELL CULTURES; SENSITIVITY; DIMETHYLBENZANTHRACENE; TOXICITY; CARCINOGENESIS; DOSE-RESPONSE RELATIONSHIPS; EMBRYOS; ENZYME ACTIVITY; HAMSTERS; METABOLITES; MICE; MUTAGENESIS; OUABAIN; SKIN; ANIMALS; AROMATICS; BODY; CARBOHYDRATES; CARDIOTONICS; CONDENSED AROMATICS; DRUGS; GLYCOSIDES; MAMMALS; ORGANIC COMPOUNDS; ORGANS; PATHOGENESIS; RODENTS; STEROIDS; STROPHANTIN; VERTEBRATES; 560301* - Chemicals Metabolism & Toxicology- Cells- (-1987); 550300 - Cytology

Citation Formats

Huberman, E., and Slaga, T.J. Mutagenicity and tumor-initiating activity of fluorinated derivatives of 7,12-dimethylbenz(a)anthracene. United States: N. p., 1979. Web.
Huberman, E., & Slaga, T.J. Mutagenicity and tumor-initiating activity of fluorinated derivatives of 7,12-dimethylbenz(a)anthracene. United States.
Huberman, E., and Slaga, T.J. Thu . "Mutagenicity and tumor-initiating activity of fluorinated derivatives of 7,12-dimethylbenz(a)anthracene". United States.
@article{osti_5059493,
title = {Mutagenicity and tumor-initiating activity of fluorinated derivatives of 7,12-dimethylbenz(a)anthracene},
author = {Huberman, E. and Slaga, T.J.},
abstractNote = {7,12-Dimethylbenz(a)anthracene (DMBA) and its 1-, 2-, 5-, and 11-fluoro derivatives were tested to determine their mutagenicity for ouabain resistance in Chinese hamster V79 cells and their tumor-initiating activity in mouse skin. Inasmuch as V79 cells do not metabolize polycyclic aromatic hydrocarbons, mutagenesis was tested both in the presence and in the absence of golden hamster embryo cells capable of metabolizing polycyclic aromatic hydrocarbons. Neither DMBA nor any of the fluorinated derivatives showed mutagenicity for V79 cells in the absence of the golden hamster cells. In the presence of these cells, DMBA and 11-fluoro-DMBA exhibited a comparable mutagenic response that was dose dependent. At a dose as low as 0.01 ..mu..m, a 7- to 10-fold increase in the frequency of ouabain-resistant mutants was observed. The other derivatives were either inactive or required more than a 1000-fold higher dose to induce a comparable mutagenic response. Similarly, both DMBA and 11-fluoro-DMBA at 100 nmol initiated tumors in 100% of the tested mice, whereas the other fluorinated derivatives at this dose initiated skin tumors in 15% or less of the treated mice. The average number of papillomas per mouse induced by 1-, 2-, and 5-fluoro-DMBA was more than 100-fold lower than the number induced by DMBA or 11-fluoro-DMBA. These results suggest that carbon positions 1 and 2 of DMBA, which are located at the bay region, and position 5, which is located at the K-region, are involved in the metabolic activation of DMBA into mutagenic and carcinogenic metabolites.},
doi = {},
journal = {Cancer Res.; (United States)},
number = ,
volume = 39,
place = {United States},
year = {1979},
month = {2}
}