Tumour induction by methyl-nitroso-urea following preconceptional paternal contamination with plutonium-239.

2.50
Hdl Handle:
http://hdl.handle.net/10541/92919
Title:
Tumour induction by methyl-nitroso-urea following preconceptional paternal contamination with plutonium-239.
Authors:
Lord, Brian I; Woolford, Lorna B; Wang, L; Stones, V A; McDonald, D; Lorimore, S A; Papworth, D; Wright, Eric G; Scott, David
Abstract:
We 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.
Affiliation:
CRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Citation:
Tumour induction by methyl-nitroso-urea following preconceptional paternal contamination with plutonium-239. 1998, 78 (3):301-11 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
Aug-1998
URI:
http://hdl.handle.net/10541/92919
PubMed ID:
9703275
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorLord, Brian Ien
dc.contributor.authorWoolford, Lorna Ben
dc.contributor.authorWang, Len
dc.contributor.authorStones, V Aen
dc.contributor.authorMcDonald, Den
dc.contributor.authorLorimore, S Aen
dc.contributor.authorPapworth, Den
dc.contributor.authorWright, Eric Gen
dc.contributor.authorScott, Daviden
dc.date.accessioned2010-02-24T13:29:09Z-
dc.date.available2010-02-24T13:29:09Z-
dc.date.issued1998-08-
dc.identifier.citationTumour induction by methyl-nitroso-urea following preconceptional paternal contamination with plutonium-239. 1998, 78 (3):301-11 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid9703275-
dc.identifier.urihttp://hdl.handle.net/10541/92919-
dc.description.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.en
dc.language.isoenen
dc.subjectExperimental Leukaemiaen
dc.subjectThymus Canceren
dc.subject.meshAnimals-
dc.subject.meshBone Marrow Cells-
dc.subject.meshCell Count-
dc.subject.meshChromosome Aberrations-
dc.subject.meshColony-Forming Units Assay-
dc.subject.meshFemale-
dc.subject.meshLeukemia, Experimental-
dc.subject.meshLymphoma-
dc.subject.meshMale-
dc.subject.meshMethylnitrosourea-
dc.subject.meshMice-
dc.subject.meshMice, Inbred CBA-
dc.subject.meshMice, Inbred DBA-
dc.subject.meshPaternal Exposure-
dc.subject.meshPlutonium-
dc.subject.meshSpermatozoa-
dc.subject.meshSpleen-
dc.subject.meshThymus Neoplasms-
dc.subject.meshTime Factors-
dc.titleTumour induction by methyl-nitroso-urea following preconceptional paternal contamination with plutonium-239.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalBritish Journal of Canceren
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