Effect of. cap alpha. -tocopherol, butylated-hydroxytoluene and hydroxy-anisole on the activation and binding of aflatoxin B/sub 1/ to macromolecules

Conference · Fri May 01 00:00:00 EDT 1987 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6119940

Ch'ih, J J; Biedrzycka, D; Devlin, T M

The anti-oxidants, ..cap alpha..-tocopherol(TPA), butylated-hydroxy-toluene(BHT) and hydroxyanisole(BHA) inhibit the carcinogenic and toxic effects of a variety of chemical compounds, their effect on aflatoxin B/sub 1/ (AFB/sub 1/) activation and binding was examined utilizing rat liver microsomes and cells. With a NADPH generating system, oxygen, microsomes, (/sup 3/H)-AFB/sub 1/, 2.2 pmoles/h/mg protein was activated and bound to macromolecules. In hepatocytes, 3.4 and 1.4 pmoles of AFB/sub 1/ per 10/sup 6/ cells were taken up and bound to macromolecules, whereas the nucleic acid fraction contained 0.19 pmoles of bound AFB/sub 1/. Moderate decreases of AFB/sub 1/ activation and binding were observed when TPA was present in both cell-free and hepatocytes systems. Only in hepatocytes, BHT inhibited the AFB/sub 1/ uptake and binding to nucleic acids. BHA, however, inhibited microsomal activation of AFB/sub 1/ by 73%; maximum inhibition was reached at 1 mM. AFB/sub 1/ uptake, and binding to nucleic acids were inhibited by 65% and 79% by BHA. GSH-transferase activity of cells treated with these agents was not altered. The effect of BHA at various concentrations on AFB activation was compared with cytochrome P-450 inhibitors; the ED/sub 50/ of SKF 525A, BHA and metyrapone was 9 uM, 80 uM and 380 uM respectively. The data suggest that TPA, BHA and BHT exert their effect by different mechanisms.

• Research Organization: Hahnemann Univ. School of Medicine, Philadelphia, PA
• OSTI ID: 6119940
• Report Number(s): CONF-870644-; TRN: 87-034178
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 46:6; Conference: 78. annual meeting of the American Society of Biological Chemists conference, Philadelphia, PA, USA, 7 Jun 1987
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
AFLATOXIN
BIOCHEMICAL REACTION KINETICS
ANISOLE
BIOLOGICAL EFFECTS
ANTIOXIDANTS
TOLUENE
ENZYME INHIBITORS
LIVER
METABOLIC ACTIVATION
MICROSOMES
MOLECULES
NUCLEIC ACIDS
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKYLATED AROMATICS
ANIMALS
ANTIGENS
AROMATICS
BODY
CELL CONSTITUENTS
DIGESTIVE SYSTEM
ETHERS
GLANDS
HYDROCARBONS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANOIDS
ORGANS
REACTION KINETICS
RODENTS
TOXIC MATERIALS
TOXINS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550501 - Metabolism- Tracer Techniques