Tissue, sex, and animal species specificity of aflatoxin B1 inhibition of nuclear RNA polymerase II activity.

Recent studies from this laboratory have shown that several chemical carcinogens, i.e., aflatoxin B1, N-OH-2-acetyl-aminofluorene, actinomycin D, and methylazoxymethanol acetate, when administered in vivo, have all produced a selective and dramatic inhibition of rat liver nuclear RNA polymerase II activity. To determine whether this inhibition is related to carcinogenesis, aflatoxin B1 is used as a model system to test tissue, sex, and animal species specificity that is known to be characteristic of carcinogenesis. The results show that aflatoxin B1 (3 mg/kg body weight, i.p., 2h) inhibits RNA polymerase II activity only in the target tissue, liver, and not in the non-target tissues, e.g., lung and brain. It inhibits liver RNA polymerase II activity preferentially in male over female rats, and has no effect on mouse liver RNA polymerase II activity. These results are in good agreement with the specificities of aflatoxin B1 carcinogenesis in the whole animal systems. Furthermore, with the four principal aflatoxins tested, the order of inhibitor effect on RNA polymerase II is: B1 greater than G1 greater than B2, G2. It is concluded, therefore, that the inhibition of RNA polymerase II activity and carcinogenesis are likely to be related and that it is theoretically sound to use this inhibition as a diagnostic tool to screen potential carcinogens.