title: Hemopoietic damage and induction of leukemia in offspring due to preconception paternal irradiation from incorporated plutonium-239.
abstract: Preconception paternal irradiation has been implicated in a localized excess of childhood leukemia and non-Hodgkin's lymphoma close to a nuclear reprocessing plant. Other epidemiological studies, however, threw doubt on the validity of this hypothesis. Experimental evidence implicating preconception paternal X rays in the development of lung and skin cancers has also been questioned. In this study, (239)Pu (0, 128 or 256 kBq kg(-1)) was injected into male CBA-H and DBA-2 mice 12 weeks before they were mated with CBA-H and C57BL/6 females. Their offspring were assessed for hematological status at 6 to 18 weeks of age or were treated with either 3.3 Gy whole-body gamma rays or methylnitrosourea (MNU, 50 mg kg(-1)) and monitored for onset of malignancies of the lymphoid and hemopoietic system. As a group, offspring were normal hematologically, but up to 35% of individual mice had femoral cellularities and numbers of spleen and fibroblastoid colony-forming cells outside the normal range. Exposure of the offspring to radiation or MNU significantly increased the rate of incidence of lymphoid and myeloid leukemias. Simulation of the experiments with preconception gamma irradiation indicated that damage to the spermatogenic stem cell was an important factor. It is concluded that preconception paternal irradiation can influence susceptibility of offspring to a subsequent exposure to a carcinogen.
authors.affiliation: CRC Section of Haemopoietic Cell and Gene Therapeutics, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, United Kingdom.
authors.forename: B I
authors.initials: BI
authors.lastname: Lord
authors.forename: K P
authors.initials: KP
authors.lastname: Hoyes
mesh_terms: D000818:Animals; D005260:Female; D006410:Hematopoiesis / Q000528:radiation effects*; D007953:Leukemia, Radiation-Induced / Q000209:etiology*; D008297:Male; D008770:Methylnitrosourea / Q000633:toxicity; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D018812:Paternal Exposure; D011005:Plutonium / Q000633:toxicity*
chemical_list: D011005:Plutonium; D008770:Methylnitrosourea