The significance of glutathione conjugation for aflatoxin B1 metabolism in rainbow trout and coho salmon.

Rainbow trout are known to be more susceptible to aflatoxin B1 (AFB1) hepatocarcinogenesis than coho salmon, or trout pre-fed the carcinogenesis inhibitors beta-naphthoflavone (beta NF), Aroclor 1254 or indole-3-carbinol. The study reported here examined the relationship between AFB1-glutathione (GSH) conjugation and AFB1 carcinogenesis in salmon, trout and trout pre-fed the three inhibitors. The AFB1-glutathione (AFB1-SG) conjugate was not detected in salmon bile and was present in trout bile in amounts representing less than 0.2% of the administered dose 24 hr after injection of [3H]AFB1. The major conjugates were glucuronides of aflatoxicol and aflatoxicol M1. In incubations of isolated liver cell fractions, less than 0.5% of the original AFB1 dose was recovered as AFB1-SG in salmon and trout preparations, compared to 25% in mouse-liver cell preparations. The GSH concentration in livers of the control trout was higher than that for coho salmon but lower than that for trout pre-fed beta NF. Liver GSH-transferase activity in control trout livers was much higher than in the control salmon livers, but was only 62% of that found for trout fed beta NF. There was no apparent relationship among the various groups between liver GSH concentrations, liver GSH-transferase activity, or biliary GSH conjugate, and the degree of carcinogenic response of AFB1. Thus current evidence does not indicate a major role for aflatoxin B1 epoxide-GSH detoxification in coho salmon, or rainbow trout fed any of the three anticarcinogens tested. These results in salmonid fish are contrary to those which suggest AFB1-SG conjugation as a major determinant of AFB1 carcinogenesis and its dietary modulation in rodent models.