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

Recent studies from this laboratory have shown that severalchemical carcinogens, i.e., aflatoxin B₁, N-OH-2-acetylaminofluorene,actinomycin D, and methylazoxymethanol acetate, when administeredin vivo, have all produced a selective and dramatic inhibitionof rat liver nuclear RNA polymerase II activity. To determinewhether this inhibition is related to carcinogenesis, aflatoxinB₁ is used as a model system to test tissue, sex, and animalspecies specificity that is known to be characteristic of carcinogenesis.The results show that aflatoxin B₁ (3 mg/kg body weight, i.p.,2 h) inhibits RNA polymerase II activity only in the targettissue, liver, and not in the non-target tissues, e.g., lungand brain. It inhibits liver RNA polymerase II activity preferentiallyin male over female rats, and has no effect on mouse liver RNApolymerase II activity. These results are in good agreementwith the specificities of aflatoxin B₁ carcinogenesis in thewhole animal systems. Furthermore, with the four principal aflatoxinstested, the order of inhibitory effect on RNA polymerase IIis: B₁ > G₁ > B₂, G₂. It is concluded, therefore, thatthe inhibition of RNA polymerase II activity and carcinogenesisare likely to be related and that it is theoretically soundto use this inhibition as a diagnostic tool to screen potentialcarcinogens.