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U.S. Department of Energy
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Studies on the anticarcinogenic action of BHA: regioselective inhibition of benzo(a)pyrene metabolism

Thesis/Dissertation ·
OSTI ID:5213211
Butylated hydroxyanisole (BHA; 2(3)-tert-butyl-4-hydroxyanisole) is a food preservative that exhibits anticarcinogenic activity. BHA added in vitro inhibited AHH activity of hepatic microsomes. The AHH activity of lung microsomes were inhibited to a lesser extent by BHA than that of hepatic microsomes. The AHH activities of liver and lung microsomes became less susceptible to the inhibition of BHA after pretreatment of the animals with 3-methylcholanthrene or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) but pretreatment with phenobarbital did not produce such an effect. Species and sex variation was not demonstrated between rats and mice. In skin homogenates, AHH activities of control rats and mice were not inhibited by BHA. The only skin sample whose AHH was inhibited by BHA is that from TCDD-treated mice. Kinetic analysis of BHA inhibiton on hepatic microsomal AHH activities indicated a mixed mechanism. BHA alters BP metabolism by direct inhibition and by altering the composition of microsomal P-450-dependent monooxygenase enzymes after chronic treatment. These changes can alter BP metabolism regioselectively in the liver and lung, a target tissue where diol epoxide formation is specifically inhibited. This provides a possible mechanism for the anticarcinogenic action of BHA.
OSTI ID:
5213211
Country of Publication:
United States
Language:
English