Possible carcinogenic effects of X-rays in a transgenerational study with CBA mice

A lifetime experiment using 4279 CBA/J mice was carried out to investigate whether the pre-conceptual exposure of sperm cells to X-ray radiation or ur ethane would result in an increased cancer risk in the untreated progeny, a nd/or increased susceptibility to cancer following exposure to a promoting agent. The study consisted of four main groups, namely a control group (sal ine), a urethane group (1 mg/g body wt) and two X-ray radiation groups (1 G y, 2 Gy), At 1, 3 and 9 weeks after treatment, the males of these four pare ntal groups were mated with untreated virgin females. The offspring of each parental group was divided into two subgroups: one received s.c. urethane (0.1 mg/g body wt once) as a promoter, the other saline, at the age of 6 we eks, All animals were evaluated for the occurrence of tumours, K-ras oncoge ne and p53 tumour suppressor gene mutations were investigated in frozen lun g tumour samples. The female offspring of male parents exposed to X-rays 1 week before their mating showed a trend towards a higher tumour incidence o f the haematopoietic system than the F1 controls. In addition, a higher per centage of bronchioloalveolar adenocarcinomas in male offspring born to irr adiated paternals mated 1 week after X-ray treatment points to a plausible increased sensitivity of post-meiotic germ cell stages towards transgenerat ional carcinogenic effects, On the other hand, no increased tumour incidenc e and malignancy were observed in the offspring born to irradiated paternal s mated 3 and 9 weeks after X-ray treatment. Paternal urethane treatment 1, 3 and 9 weeks prior to conception did not result in significantly altered incidence or malignancy of tumours of the lung, liver and haematopoietic ti ssue in the offspring. K-rns mutations increased during tumour progression from bronchioloalveolar hyperplasia to adenoma, Codon 61 K-ras mutations we re more frequent in lung tumours of urethane-promoted progeny from irradiat ed parents than from control parents. P53 mutations were absent from these lung alterations.