Document Detail

Food restriction increases detoxification of polycyclic aromatic hydrocarbons in the rat.
MedLine Citation:
PMID:  1576702     Owner:  NLM     Status:  MEDLINE    
It is well known that food restriction diminishes tumor formation, but mechanisms responsible are difficult to define because multiple physiological changes result from dietary alterations. Studies in this report were designed to focus specifically on the effects of food restriction on hepatic metabolism of polycyclic aromatic hydrocarbons following liver transplantation. By placing livers from food-restricted and untreated rats into naive controls, the effects of diet could be restricted to the liver. After a 15 min infusion of [3H]benzo[a]pyrene under these conditions, food restriction increased polar metabolites in liver (70 pmol/g) and blood (8 pmol/ml) compared to controls approximately 2-fold. Four hours after liver transplantation, levels of polar metabolites in blood were diminished by approximately 50% but were still approximately 2-fold higher in the food-restricted than in the control group. Lung, kidney, spleen, adrenal, ovary, colon, heart and brain also contained higher levels of polar metabolites in the food-restricted than in the control group. The more hydrophobic glucuronides and sulfate conjugates accounted for most of the elevation in polar metabolites in blood from the food-restricted group. In spite of the increase in circulating metabolites in blood of food-restricted animals, DNA binding in liver, lung and kidney was identical in tissues from control and food-restricted groups. In order to evaluate the hypothesis that food restriction stimulated the release of hepatic benzo[a]pyrene metabolites, a liver perfusion model was employed. Maximal rates of release of polar metabolites into the effluent perfusate were approximately 30 and approximately 45 nmol/g/h in livers of control and food-restricted rats respectively. Moreover, rates of metabolism of the model compound p-nitroanisole and glucuronidation of p-nitrophenol were also approximately 2-fold higher in livers from food-restricted than control rats. However, rates of monooxygenation were the same in microsomes prepared from livers of food-restricted or control animals. These results support the hypothesis that food restriction enhances the supply of cofactors which stimulate metabolism of polycyclic aromatic hydrocarbons. This detoxification process may be an important mechanism involved in the protective action of reduced food intake.
K L Wall; W Gao; W Qu; G Kwei; F C Kauffman; R G Thurman
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Carcinogenesis     Volume:  13     ISSN:  0143-3334     ISO Abbreviation:  Carcinogenesis     Publication Date:  1992 Apr 
Date Detail:
Created Date:  1992-06-05     Completed Date:  1992-06-05     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  519-23     Citation Subset:  IM    
Department of Pharmacology, University of North Carolina, Chapel Hill 27599.
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MeSH Terms
Benzo(a)pyrene / metabolism
Carcinogens / metabolism*
Diet, Reducing*
Glucuronates / metabolism
Metabolic Detoxication, Drug
Polycyclic Compounds / metabolism*
Rats, Inbred Strains
Grant Support
Reg. No./Substance:
0/Carcinogens; 0/Glucuronates; 0/Polycyclic Compounds; 50-32-8/Benzo(a)pyrene

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