A comparison of the changes induced in rat liver by feeding low levels of aflatoxin B1 or an azo dye.

(1) Rats have been given 6 weeks' feeding with low levels of the hepatocarcinogens aflatoxin B1 and 2-methyl dimethyl aminoazobenzene (2-Me-DAB). (2) It has been confirmed that 3 weeks' feeding with either toxin is sub-carcinogenic, whereas 6 weeks' feeding results in a high incidence of hepatocarcinoma. (3) The changes occurring in the liver during this feeding have been monitored by histological examination and zonal rotor centrifugation. (4) Marked similarities have been observed between the time courses of development of changes induced in the liver by the two carcinogens. Little change is observed after 2 weeks' feeding with the toxins. The greatest change occurs after 3 weeks' feeding, which results in tissue necrosis and the loss of a large proportion of the tetraploid hepatocyte nuclei. (5) A compensatory proliferation of predominantly diploid hepatocytes takes place in the presence of a continuing supply of either of the carcinogens. This indicates that not only does feeding each carcinogen induce the production of a population of hepatocytes resistant to the cytotoxicity of the inducing agent, but that the population is also resistant to the cytotoxicity of the other carcinogen.