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

Purpose: To investigate the effects of preconception paternal irradiation ( PPI) from injected Pu-239 On the susceptibility to induction of lympho-haem opoietic malignancy by subsequent irradiation or exposure to a chemical car cinogen. Materials and Methods: The male CBA/H and DBA2 mouse was injected with 0, 1 28 or 256 Bq g(-1) Pu-239 12 weeks before mating with the normal CBA/H and C57B1 female respectively. CBA/H offspring were exposed to 3.3 Gy gamma-ray s total body irradiation: BDF1 offspring were injected with 50 mg kg(-1) me thyl nitrosourea (MNU). The offspring were assayed for changes in bone marr ow 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 cellula rity, spleen colony-forming units (CFU-S) and fibroblastoid colony-forming units (CFU-F), significant numbers of PPI offspring presented levels outsid e the normal range. There was a tendency for them also to show increased, d ose-related, levels of chromosomal aberrations. Offspring treated with irra diation or MNU developed an increased incidence of lymphohaemopoietic malig nancies. Conclusions: These studies have shown that PPI results in offspring that ar e more susceptible to the induction of lymphohaemopoietic malignancy on enc ountering a secondary carcinogenic insult. This may be linked to inherited chromosomal instability and abnormal kinetics of haemopoiesis. The experime nts indicate a potential mechanism by which an increased incidence of leuka emia may be linked to PPI.