The Effect of Variations in LET and Cell Cycle on Radiation Hepatocarcinogenesis

The effect of variations in LET and cell cycle on radiation carcinogenesis was studied in${\rm LAF}_{1}/\text{Jax}$mouse liver. Our results are consistent with those of Cole and Nowell in that both the quality (LET) of the radiation and the addition of a proliferative stimulus significantly alter the hepatocarcinogenic endpoint. A single, whole-body, 200-rad dose of137Cs gamma rays increased the hepatoma incidence by approximately 3- to 4-fold over the control rates, when a pure proliferative stimulus (partial hepatectomy) was added. Also a single, whole-body, 200-rad dose of fission neutron irradiation increased the hepatoma incidence by approximately 6 -to 9-fold over the control rate, when combined with partial hepatectomy. Furthermore, both the137Cs and fission neutron hepatocarcinogenic rates were enhanced regardless of whether the irradiation was given either during liver regeneration or 8-13 weeks prior to partial hepatectomy. However, neither137Cs nor fission neutron irradiation alone (i.e., without partial hepatectomy), significantly increased the incidence of hepatomas. The highest incidence of hepatomas observed was nine times the unirradiated control incidence and 50% greater than that in the next highest experimental groups, and occurred in mice irradiated with fission neutrons 24 hours after partial hepatectomy. The difference between this group and those irradiated with neutrons 36.5 and 43.5 hours after hepatectomy was not, however, statistically significant. These and other data indicate nonetheless that the role of the cell cycle phase in susceptibility to carcinogenesis warrants further investigation.