Elevation of serum Phase II enzymes by anticarcinogenic enzyme inducers: markers for a chemoprotected state?
| Autor: | Christabel L. Fernandes, Hans J. Prochaska |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Adult
Cancer Research Dimethyl Fumarate Butylated Hydroxyanisole Pharmacology Reductase Mice chemistry.chemical_compound Fumarates Oltipraz NAD(P)H Dehydrogenase (Quinone) Animals Anticarcinogenic Agents Humans Enzyme inducer Anticarcinogen Carcinogen Glutathione Transferase chemistry.chemical_classification biology General Medicine Glutathione Mice Inbred C57BL Enzyme chemistry Biochemistry Enzyme Induction biology.protein Female Butylated hydroxyanisole |
| Zdroj: | Carcinogenesis. 14:2441-2445 |
| ISSN: | 1460-2180 0143-3334 |
| Popis: | Inducers of Phase II enzymes, already consumed by humans as food additives, medicines or as constituents of vegetables, can prevent experimental carcinogenesis. Since protection is neither carcinogen- nor organ-specific, clinical trials are already underway to establish the efficacy of 'anticarcinogenic enzyme inducers' (i.e. oltipraz). However, efficient and cost-effective assays to establish the dose wherein a putative anticarcinogen can raise Phase II enzyme levels are lacking. We tested the proposal that serum Phase II enzyme activities would be dependent on relative tissue levels by measuring quinone reductase and glutathione S-transferase activities in sera of mice treated with dietary 2(3)-tert-butyl-4-hydroxyanisole (BHA) or dimethyl fumarate. Serum activities were significantly elevated in animals with increased tissue specific activities of these Phase II enzymes. Increasing concentrations of BHA in the diet from 0.05-0.5% increased hepatic specific activities of both QR and GST from two to six-fold, and increases in serum activities were well correlated to increases observed in the liver (r2 > or = 0.95). There was no evidence for an elevation of serum alanine aminotransferase levels. Thus, in the absence of serological evidence for hepatocellular damage, increased serum Phase II enzyme activities can be correlated to tissue levels. Our results suggest that similar assays tailored to human sera will not only be useful in the execution of chemoprevention trials, but also to assess the role that Phase II enzyme induction plays in the prevention of cancer by fruits and vegetables. |
| Databáze: | OpenAIRE |
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