Journal Article

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

U. Mohr, C. Dasenbrock, T. Tillmann, M. Kohler, K. Kamino, G. Hagemann, G. Morawietz, E. Campo, M. Cazorla, P. Fernandez, L. Hernandez, A. Cardesa and L. Tomatis

in Carcinogenesis

Volume 20, issue 2, pages 325-332
Published in print February 1999 | ISSN: 0143-3334
Published online February 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.2.325
Possible carcinogenic effects of X-rays in a transgenerational study with CBA mice

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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 urethane would result in an increased cancer risk in the untreated progeny, and/or increased susceptibility to cancer following exposure to a promoting agent. The study consisted of four main groups, namely a control group (saline), a urethane group (1 mg/g body wt) and two X-ray radiation groups (1 Gy, 2 Gy). At 1, 3 and 9 weeks after treatment, the males of these four parental 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 weeks. All animals were evaluated for the occurrence of tumours. K-ras oncogene and p53 tumour suppressor gene mutations were investigated in frozen lung 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 of the haematopoietic system than the F1 controls. In addition, a higher percentage of bronchiolo-alveolar adenocarcinomas in male offspring born to irradiated paternals mated 1 week after X-ray treatment points to a plausible increased sensitivity of post-meiotic germ cell stages towards transgenerational carcinogenic effects. On the other hand, no increased tumour incidence and malignancy were observed in the offspring born to irradiated paternals 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 tissue in the offspring. K-ras mutations increased during tumour progression from bronchiolo-alveolar hyperplasia to adenoma. Codon 61 K-ras mutations were more frequent in lung tumours of urethane-promoted progeny from irradiated parents than from control parents. P53 mutations were absent from these lung alterations.

Keywords: DEN, diethylnitrosamine; H & E, haematoxylin and eosin; PCR–RFLP, polymerase chain reaction–restriction fragment length polymorphism; SSCP, single-strand conformation polymorphism.

Journal Article.  7476 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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