Inhibition of aflatoxin B1 -hepatocarcinogenesis in rats by {beta}-naphthoflavone |
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Authors: | Gurtoo HL; Koser PL; Bansal SK; Fox HW; Sharma SD; Mulhern AI; Pavelic ZP |
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Institution: | Grace Cancer Drug Center, Roswell Park Memorial Institute, New York State Department of Health 666 Elm Street, Buffalo, NY 14263, USA |
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Abstract: | Effects of ß-naphthonflavoe (ßNF) on theactivity of hepatic microsomal aflatoxin B1 (AFB1)-4-hydroxylase- the cytochrome P-450-dependent enzyme system which catalyzesthe metabolism of AFB1 to AFM1 - and on AFB1 induced in vivohepatocarcinogenesis were investigated in weanling male Fischerrats. A single i.p. injection of ßNF in doses of 20mg/kg and 150 mg/kg induced AFB1 -4-hydroxylase 3- and 4-fold,respectively, 48 h post injection. Feeding of diet containing0.01% ßNF for a period of 9-weeks induced AFB1 2-fold.AFB1, given by intubatlon in a dose of 25 µg five times/weekfor 8 weeks, produced 42 weeks later a 100% incidence of liverlesions (neoplastic foci, nodules or tumors), but feeding ßNFin diet at a con centration of 0.015% for one week prior toand during the 8 weeks of AFB treatment inhibited AFB1 hepatocarcinogenesis by -7%. These results are in accord with the suggestionthat AFB1 induction may be associated with the inhibition ofAFB1 carcinogenesis, possibly occurring as a consequence ofaccelerated detoxi-fication of AFB1 via its conversion to AFM1 |
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