Induction of lympho-haemopoietic malignancy: impact of preconception paternal irradiation.

Abstract

PURPOSE: To investigate the effects of preconception paternal irradiation (PPI) from injected 239Pu on the susceptibility to induction of lympho-haemopoietic malignancy by subsequent irradiation or exposure to a chemical carcinogen. MATERIALS AND METHODS: The male CBA/H and DBA2 mouse was injected with 0, 128 or 256 Bqg(-1) 239Pu 12 weeks before mating with the normal CBA/H and C57B1 female respectively. CBA/H offspring were exposed to 3.3 Gy gamma-rays total body irradiation: BDF1 offspring were injected with 50 mg kg(-1) methyl nitrosourea (MNU). The offspring were assayed for changes in bone marrow progenitor cell numbers and chromosome aberrations and were followed up for subsequent induction of neoplasia. RESULTS: While the untreated mouse showed a normal distribution for cellularity, spleen colony-forming units (CFU-S) and fibroblastoid colony-forming units (CFU-F), significant numbers of PPI offspring presented levels outside the normal range. There was a tendency for them also to show increased, dose-related, levels of chromosomal aberrations. Offspring treated with irradiation or MNU developed an increased incidence of lympho-haemopoietic malignancies. CONCLUSIONS: These studies have shown that PPI results in offspring that are more susceptible to the induction of lymphohaemopoietic malignancy on encountering a secondary carcinogenic insult. This may be linked to inherited chromosomal instability and abnormal kinetics of haemopoiesis. The experiments indicate a potential mechanism by which an increased incidence of leukaemia may be linked to PPI.