Early change in mitochondrial monoamine oxidase activity of rat liver during 2-acetylaminofluorene feeding.
The activities of mitochondrial type A and B monoamine oxidase were determined in the liver of rats fed a diet containing 2-acetylaminofluorene (AAF). Three days after the initiation of AAF-feeding, there was a significant decrease of type B monoamine oxidase activity without affect on type A enzyme. The decreased activity of type B monoamine oxidase, which reached a minimum after three weeks, was sustained for as long as AAF-feeding was continued. Sex-related difference in response to AAF was seen in the rat with respect to the onset and the intensity of the decreased type B monoamine oxidase activity, male rats being more sensitive to the carcinogen than female rats. In contrast to the in vivo effect, AAF showed a potent inhibitory effect on type A monoamine oxidase, rather than on type B enzyme, when added in vitro. The pI50 values were estimated to be 7.5 against type A monoamine oxidase and 4.1 against type B enzyme, respectively. The in vitro inhibition of both types of monoamine oxidase by AAF was competitive. The Ki values for AAF were calculated to be 9.51 x 10(-9)M for type A monoamine oxidase and 1.30 x 10(-5)M for type B enzyme, respectively. In accordance with the potent inhibitory effect of AAF on type A monoamine oxidase in vitro, a single administration of the carcinogen, at a dose of 50 mg/kg, resulted in a marked and temporal decrease of the enzyme activity in the mitochondria of male rat liver. Recovery of the decreased type B monoamine oxidase activity was slow, and the enzyme activity did not return to control levels, even if rats were fed the basal diet for 2 or 4 weeks after the cessation of AAF-feeding
D015073:2-Acetylaminofluorene / Q000633:toxicity*; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors; D051381:Rats; D012737:Sex Factors
D008996:Monoamine Oxidase Inhibitors; D015073:2-Acetylaminofluorene; D008995:Monoamine Oxidase