Tumour induction by methyl-nitroso-urea following preconceptional paternal contamination with plutonium-239.
AuthorsLord, Brian I
Woolford, Lorna B
Stones, V A
Lorimore, S A
Wright, Eric G
AffiliationCRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
MetadataShow full item record
AbstractWe have investigated the possibility that transgenerational effects from preconceptional paternal irradiation (PPI) may render offspring more vulnerable to secondary exposure to an unrelated carcinogen. 239Pu (0, 128 or 256 Bq g(-1)) was administered by intravenous injection to male mice, 12 weeks before mating with normal females. Two strains of mouse were used -- CBA/H and BDF1. Haemopoietic spleen colony-forming units (CFU-S) and fibroblastoid colony-forming units (CFU-F), a component of their regulatory microenvironment, were assayed independently in individual offspring at 6, 12 and 19 weeks of age. Bone marrow and spleen from each of these mice were grown in suspension culture for 2 or 7 days for assessment of chromosomal aberrations. Female BDF1 were injected with methyl-nitroso-urea (MNU) as a secondary carcinogen at 10 weeks of age and monitored for onset of leukaemia/lymphoma. Mean values of CFU-S and CFU-F were unaffected by preconceptional paternal plutonium-239 (PP-239Pu), although for CFU-F in particular there was an apparent increase in variation between individual animals. There was significant evidence of an increase in chromosomal aberrations with dose in bone marrow but not in spleen. By 250 days, 68% of MNU-treated control animals (no PPI) had developed thymic lymphoma (62%) or leukaemia (38%). The first case arose 89 days after MNU administration. In the groups with PPI, leukaemia/lymphoma developed from 28 days earlier, rising to 90% by 250 days. Leukaemia (65%) now predominated over lymphoma (35%). This second generation excess of leukaemia appears to be the result of PPI and may be related to inherited changes that affect the development of haemopoietic stem cells.
CitationTumour induction by methyl-nitroso-urea following preconceptional paternal contamination with plutonium-239. 1998, 78 (3):301-11 Br. J. Cancer
JournalBritish Journal of Cancer
- Induction of lympho-haemopoietic malignancy: impact of preconception paternal irradiation.
- Authors: Lord BI, Woolford LB, Wang L, McDonald D, Lorimore SA, Stones VA, Wright EG, Scott D
- Issue date: 1998 Dec
- Hemopoietic damage and induction of leukemia in offspring due to preconception paternal irradiation from incorporated plutonium-239.
- Authors: Lord BI, Hoyes KP
- Issue date: 1999 Dec
- Tumor induction by methyl-nitroso-urea following preconceptional paternal contamination with plutonium-239.
- Authors: Little MP, Charles MW
- Issue date: 1999 May
- Strain differences in carcinogenic and hematopoietic responses of mice after injection of plutonium citrate.
- Authors: Oghiso Y, Yamada Y
- Issue date: 2000 Oct
- Reasons it is doubtful that preconceptional paternal irradiation with plutonium-239 had any effect on cancer induction by methyl-nitroso-urea.
- Authors: Selby PB
- Issue date: 1999 Nov