Reduction of a 7,12-dimethylbenz[a]anthracene DNA adduct in rat mammary tissue in vivo when pretreated with tamoxifen.
Tamoxifen (TAM), an antiestrogenic compound, has been approved for the treatment of breast cancer in high risk women. TAM has been shown to be an effective agent for prevention of breast cancer in women of varying degrees of risk and has been proposed to be used prophylactically in women whose genetic background suggests a high risk for breast cancer. However, it is not known whether TAM given prophylactically will alter the response of women to carcinogens from common environmental exposures such as tobacco smoke. Therefore, we studied the effects of TAM pretreatment on mammary DNA adducts of the model carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA), in the female rats to assess whether TAM would alter the adduct pattern of DMBA. TAM (0.3 mg/day) was given for 7 days prior to a single 20 mg DMBA gavage treatment that is considered a carcinogenic dose in the rat. At 7 days post-DMBA, there was a reduction in the major DMBA-DNA adduct and a significant reduction in the minor DMBA-DNA adduct in mammary glands (P=0.002) of TAM pretreated rats compared to control rats. These data indicate that TAM may alter either metabolic steps in the formation of DNA binding species and/or enhance adduct removal. These data suggest that TAM given to women prior to the development of breast cancer may modulate the impact of environmental exposures, for example, tobacco smoke. Furthermore, research is needed to determine if modulation will be positive, or negative as in the current study.
Warshawsky
David
D
Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267-0056, USA. warshad@uc.edu
Dowty
Heather V
HV
LaDow
Kathy
K
Succop
Paul
P
Talaska
Glenn
G
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001345:Autoradiography; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D018736:DNA Adducts / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006868:Hydrolysis; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D018736:DNA Adducts; D013629:Tamoxifen; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA