Mildred K. Buening

7,8-Benzoflavone stimulates the metabolic activation of aflatoxin B1 to mutagens by human liver

Abstract The addition of 7,8-benzoflavone to a monooxygenase system from human liver markedly stimulated the metabolic activation of aflatoxin B 1 to mutagens. When 7,8-benzoflavone (5 × 10 −5 M) was added to this monooxygenase system, the amount of aflatoxin B 1 needed for a mutagenic response was decreased by 20- to 40-fold. 7,8-Benzoflavone did not stimulate the metabolic activation of aflatoxin B 1 to mutagens when rat liver was used as a source of monooxygenase.

Activation of monooxygenases in human liver by 7,8-benzoflavone

Addition of 10‐4 M 7,8‐benzojlavone to homogenates of human liver samples obtained by autopsy or surgical biopsy increased the rate of benzo [a] pyrene hydroxylation up to II‐fold. 7,8‐Benzojlavone also increased the rates of hydroxylation of zoxazolamine and antipyrine at 10‐4 M but inhibited these reactions at 10‐6 M. The effects of 7,8‐benzojlavone on the hydroxylation of benzo[a]pyrene and zoxazolamine in microsomes from human liver were similar to those in homogenates. Addition of 7,8‐benzojlavone to homogenates of surgical biopsy samples of human liver had little or no effect on the rates of oxidative metabolism of 7‐ethoxycoumarin, coumarin, and hexobarbital. Marked individuality for the activating and inhibiting effects of 7,8‐benzojlavone was observed in different liver samples. This individuality may result both from the presence of multiple monooxygenases in varying amounts and proportions in the different liver samples and from a selective effect of 7,8‐benzojlavone on certain of the monooxygenases.