Effect of dose on the inhibition of carcinogenesis/mutagenesis by aroclor 1254 in rainbow trout fed aflatoxin B₁

Abstract

Prior studies have shown that Aroclor 1254 (PCB) differentially alters the incidence of aflatoxin B ₁ (AFB ₁ ) induced hepatocellular carcinomas in trout, depending upon the time of PCB administration relative to AFB ₁ exposure (Shelton et al., 1983). When fed simultaneously with AFB ₁ , PCB inhibits carcinoma incidence. We investigated the effect of AFB ₁ and PCB dose on this inhibition. Duplicate tanks of 100 rainbow trout were fed AFB ₁ at concentrations of 1, 4, or 8 ppb, either with or without the addition of 50 ppm PCB. Other groups were fed 4 ppb AFB ₁ + 5 ppm PCB, 50 ppm PCB alone, or control diet alone. After 9 and 12 mo, 40 and 60 fish per tank, respectively, were sampled to determine the incidence of liver tumors. The results show a parallel Inhibition of the AFB ₁ ‐tumor dose‐response curve by the presence of 50 ppm PCB. Fish fed 4 ppb AFB ₁ + 5 ppm PCB showed slight inhibition in response when compared with 4ppb AFB ₁ alone. Also, livers from fish fed 50 ppm PCB were used to prepare S20 for use in the Salmonella mutagenesis assay. These livers were less efficienct in converting AFB ₁ to a mutagen, when compared to control S20. The AFB ₁ ‐mutagenesis dose‐response curve was again shifted parallel to the right of the curve generated using control S20. These results suggest that the inhibitory action is at least partly at the level of carcinogen activation. The finding of parallel, as opposed to proportional, inhibition with varying carcinogen exposure for certain classes of inhibitors may have important implications for inhibition of environmental carcinogenesis at low levels of carcinogen exposure.