Accelerated induction of hepatomas in fast neutron irradiated mice injected with carbon tetrachloride.

Abstract

Young adult (C57L x A)F/sub 1/ hybrid mice received a single whole--body exposure to fission spectrum fast neutrons (165 to 306 rad). Subgroups of these mice then received a single subcutaneous injection of CCl/sub 4/, given either at 2, 12, 15, or 18 months post-irradiation. Control non-irradiated mice received a single injection of CCl/sub 4/. Other groups of mice were exposed to a single 500 rad dose of 250KVP x rays. The incidence of hepatomas was markedly increased in the neutron-irradiated mice (19%) as compared with that in the x-irradiated mice (2%). In the neutronirradiated mice injected with CCl/sub 4/, the hepatoma incidence attained a value of 61%, three times that in the mice irradiated with neutrons only. In addition, marked pleomorphism and atypicality of liver cell nuclei were evident in almost all of the neutron-CCl/sub 4/ mice, but were observed in only 6 of the 47 mice exposed to neutrons only. Of the small group of mice which received CCl/sub 4/ but no irradiation, and sacrificed up to 22 months later, none exhibited hepatomas or nuclear abnormalities. In this system therefore, CCl/sub 4/ seems to act as a promoting agent in liver carcinogenesis. These findings, taken together with othermore » data in the literature, support the concept that hepatoma induction is accelerated as a consequence of the action of a specific proliferative stimulus on cells bearing a latent radiation-induced alteration. The general question of the role of proliferative stimuli in radiation carcinogenesis is discussed. (auth)« less