Influence of Dietary Protein Intake on the Molecular Aspects of 7,12-Dimethylbenz(a)anthracene Induced Mammary Carcinogenesis (Cancer, Liver)
Singletary, Keith William
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Permalink
https://hdl.handle.net/2142/77455
Description
Title
Influence of Dietary Protein Intake on the Molecular Aspects of 7,12-Dimethylbenz(a)anthracene Induced Mammary Carcinogenesis (Cancer, Liver)
Author(s)
Singletary, Keith William
Issue Date
1986
Department of Study
Food Science
Discipline
Food Science
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Health Sciences, Nutrition
Language
eng
Abstract
The influence of prior protein intake in rats on the metabolism and DNA-binding of 7,12-dimethylbenz(a)anthracene (DMBA) by their isolated mammary epithelial cell aggregates was examined. DMBA was metabolized to bay-region anti- and syn- dihydrodiol-epoxides that bound to deoxyadenosine and deoxyguanosine of mammary cell DNA. During the initial 24 hours of incubation of the mammary cells, production of the syn- stereoisomer increased in a linear fashion. The production of the anti- dihydrodiol-epoxide increased rapidly following a 6-hour delay and was inhibited by actinomycin D. Rats were fed diets containing 7.5 or 15% protein supplied as casein. Restricting the protein intake of rats resulted in a decrease in metabolism and binding of DMBA to DNA in the isolated mammary cells after 6 hours of incubation. The syn- dihydrodiol-epoxide DMBA:deoxyadenosine adduct predominated in mammary cells from rats fed either concentration of protein. The quantity of extracellular water-soluble metabolites amounted to only 14% of total metabolism at 6 hours.
The effect of prior protein intake in rats on the production and release of reactive DMBA metabolites by their isolated hepatocytes was also examined. In initial studies using rat liver S9 preparations, decreasing prior protein intake resulted in increased production of mutagenic DMBA metabolites by the respective S9 preparations as indicated by increased reversion of Salmonella typhimurium. Restricting protein intake decreased extracellular water-soluble metabolites of DMBA and enhanced the binding of DMBA to extracellular DNA. Binding that occurred with hepatocyte DNA and extracellular calf-thymus DNA was due to bay-region dihydrodiol-epoxides of DMBA and five unidentified adducts. The present studies show that dietary protein can modify carcinogen metabolism and adduct formation. However, the specific effect depends on the tissue examined. These studies suggest that the increased incidence of DMBA-induced mammary tumors in rats fed a low protein diet prior to administration of DMBA is possibly related to changes in the liver metabolism of this carcinogen rather than changes in the target mammary cells.
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