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Influence of vitamins A, C, and E and β‐carotene on aflatoxin B 1 binding to DNA in woodchuck hepatocytes
Author(s) -
Yu MingWhei,
Zhang YuJing,
Blaner William S.,
Santella Regina M.
Publication year - 1994
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19940201)73:3<596::aid-cncr2820730316>3.0.co;2-n
Subject(s) - ascorbic acid , anticarcinogen , vitamin , micronutrient , vitamin c , biochemistry , aflatoxin , vitamin e , carcinogen , glutathione , chemistry , antioxidant , microbiology and biotechnology , in vitro , biology , food science , enzyme , biological activity , organic chemistry
Abstract Background. There is extensive epidemiologic evidence suggesting a protective role for micronutrients in cancer incidence. This evidence comes from studies of fruit and vegetable intake and serum levels of specific micronutrients. There also is limited in vitro evidence demonstrating that micronutrients can influence the first step in carcinogenesis, binding of chemical carcinogens to DNA. These in vitro studies allow the determination of specific effects of individual micronutrients. The influence of micronutrients on DNA binding of aflatoxin B1 (AFB 1 ), a potent hepatocarcinogen, in mammalian cells is unknown. Woodchuck hepatocytes were used as a model to investigate the effects of vitamin A (all‐ trans retinol), C (ascorbic acid), ascorbyl palmitate (a synthetic lipophilic derivative of ascorbic acid), vitamin E (α‐to‐copherol), and β‐carotene on AFB 1 ‐DNA binding. Methods. Woodchuck hepatocytes were treated with 4 doses (0.080, 0.40, 2.0, and 10 μM) of [ 3 H]AFB 1 or with different combinations of AFB 1 and the vitamins for 6 hours, and adduct levels determined. Western blot analysis of protein extracts of treated cells was used to determine the effects of vitamin A and β‐carotene on glutathi‐one‐S‐transferase M1 levels. Results. Vitamin A inhibited formation of AFB 1 ‐DNA adducts in a dose‐dependent manner throughout a concentration range of 34–112 μM by 40–80%. Vitamin C (0.080–10 mM) was much less effective than vitamin A as an inhibitor of AFB 1 ‐DNA binding. Treatment with 6.0–48.3 μM ascorbyl palmitate reduced adduct levels at lower AFB 1 concentrations but had no significant effect at higher AFB 1 concentrations. β‐Carotene and vitamin E enhanced covalent binding of AFB 1 to DNA. Enhancement with β‐carotene was observed when both tetrahydrofuran or liposomes were used as the administration vehicle. Western blot analysis indicated that neither the vitamin A nor β‐carotene treatment affected glutathione‐S‐transferase M1 protein levels. Conclusions. These results demonstrate that micronutrients play a complex role in the process of chemical carcinogenesis. Although protective effects were seen with several antioxidant vitamins, increased DNA adduct formation was observed with β‐carotene and vitamin E. This antioxidant activity may be unrelated to the inhibition of DNA adduct formation. Additional studies are needed to understand the mechanism of enhanced adduct formation.