Promotion of skin tumors by 12-O-tetradecanoylphorbol-13-acetate in two generations of descendants of male mice exposed to X-ray irradiation.

Progeny of outbred SHR male mice intact or exposed to a single dose of whole-body X-ray irradiation (4.2 Gy) was painted twice a week for 24 weeks from the age of 4 months with acetone or with acetone solution of 6.15 micrograms 12-O-tetradecanoylphorbol-13-acetate (TPA). The incidence and number of skin papillomas were monitored from 2 until 20 weeks after the last application of the promoter. Exposure to acetone was never followed by skin tumor development in the progeny of either irradiated or non-irradiated males. Two weeks after TPA treatment in the progeny of intact mice the incidence of skin tumors was 20.1% in males and 36.6% in females, and 20 weeks later it was 11.6% in males and 14.6% in females. The skin tumor incidence in the progeny of the irradiated male mice 2 and 20 weeks after the last painting was 75.0% and 67.5% in males, 50.0% and 42.5% in females, respectively. Some F1 offspring of the irradiated male mice were mated before the start of TPA treatment, and F2 progeny were exposed to acetone or TPA as F1. The incidence of skin papilloma 2 weeks after the last TPA painting was 57.8% in males and 40.0% in females, whereas at 20 weeks after the last exposure to promoter it was 53.3% and 35.6%, respectively. In the progeny of irradiated male mice there were more animals with multiple (> 4) skin papillomas than in the progeny of intact mice. Our data allow us to suggest that irradiation of males before mating increases the susceptibility of progeny of at least two generations to promoters of carcinogenesis due to persisting genome instability.