Transgenerational effects of preconception paternal contamination with (55)Fe.

2.50
Hdl Handle:
http://hdl.handle.net/10541/85614
Title:
Transgenerational effects of preconception paternal contamination with (55)Fe.
Authors:
Hoyes, Katherine P; Lord, Brian I; McCann, Christine; Hendry, Jolyon H; Morris, Ian D
Abstract:
The conjecture that germline mutations induced by radiation exposure before conception may predispose subsequent offspring to cancer remains contentious. Previous experimental studies have shown that preconception paternal irradiation with (239)Pu induces perturbations in the hemopoietic systems of offspring and influences sensitivity to a secondary carcinogen. In the present study, male DBA2 mice were injected intravenously with the Auger electron emitter (55)Fe (4 kBq g(-1)) 18 or 84 days before mating with normal females. Comet analysis showed an increased incidence of DNA strand breaks in sperm from contaminated animals after 84 days, but not after 18 days, indicating spermatogonial rather than spermatid damage. Offspring were either assayed for changes in bone marrow stem cells and committed progenitors or challenged with the chemical carcinogen methyl nitrosourea (MNU, 50 mg/kg) at 10 weeks of age and monitored for the onset of malignancy. Offspring from irradiated fathers had normal peripheral blood profiles, although the stem cell population was amplified in offspring arising from those exposed to (55)Fe at 84 days before conception. Exposure to MNU significantly increased the incidence of lympho-hemopoietic malignancies in offspring from the 84-day group, but not in those from the 18-day group. These findings support the hypothesis that aberrations that are potentially leukemogenic may be transmitted to offspring after radiation damage to the paternal germline.
Affiliation:
Cancer Research Campaign Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, M20 4BX, United Kingdom.
Citation:
Transgenerational effects of preconception paternal contamination with (55)Fe. 2001, 156 (5 Pt 1):488-94 Radiat. Res.
Journal:
Radiation Research
Issue Date:
Nov-2001
URI:
http://hdl.handle.net/10541/85614
PubMed ID:
11604061
Type:
Article
Language:
en
ISSN:
0033-7587
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorHoyes, Katherine Pen
dc.contributor.authorLord, Brian Ien
dc.contributor.authorMcCann, Christineen
dc.contributor.authorHendry, Jolyon Hen
dc.contributor.authorMorris, Ian Den
dc.date.accessioned2009-11-06T16:46:47Z-
dc.date.available2009-11-06T16:46:47Z-
dc.date.issued2001-11-
dc.identifier.citationTransgenerational effects of preconception paternal contamination with (55)Fe. 2001, 156 (5 Pt 1):488-94 Radiat. Res.en
dc.identifier.issn0033-7587-
dc.identifier.pmid11604061-
dc.identifier.urihttp://hdl.handle.net/10541/85614-
dc.description.abstractThe conjecture that germline mutations induced by radiation exposure before conception may predispose subsequent offspring to cancer remains contentious. Previous experimental studies have shown that preconception paternal irradiation with (239)Pu induces perturbations in the hemopoietic systems of offspring and influences sensitivity to a secondary carcinogen. In the present study, male DBA2 mice were injected intravenously with the Auger electron emitter (55)Fe (4 kBq g(-1)) 18 or 84 days before mating with normal females. Comet analysis showed an increased incidence of DNA strand breaks in sperm from contaminated animals after 84 days, but not after 18 days, indicating spermatogonial rather than spermatid damage. Offspring were either assayed for changes in bone marrow stem cells and committed progenitors or challenged with the chemical carcinogen methyl nitrosourea (MNU, 50 mg/kg) at 10 weeks of age and monitored for the onset of malignancy. Offspring from irradiated fathers had normal peripheral blood profiles, although the stem cell population was amplified in offspring arising from those exposed to (55)Fe at 84 days before conception. Exposure to MNU significantly increased the incidence of lympho-hemopoietic malignancies in offspring from the 84-day group, but not in those from the 18-day group. These findings support the hypothesis that aberrations that are potentially leukemogenic may be transmitted to offspring after radiation damage to the paternal germline.en
dc.language.isoenen
dc.subjectRadiation-Induced Leukaemiaen
dc.subject.meshAnimals-
dc.subject.meshBlood Cell Count-
dc.subject.meshDNA Damage-
dc.subject.meshFetus-
dc.subject.meshIron Radioisotopes-
dc.subject.meshLeukemia, Radiation-Induced-
dc.subject.meshMale-
dc.subject.meshMethylnitrosourea-
dc.subject.meshMice-
dc.subject.meshMice, Inbred DBA-
dc.subject.meshPaternal Exposure-
dc.subject.meshSpermatozoa-
dc.subject.meshTestis-
dc.titleTransgenerational effects of preconception paternal contamination with (55)Fe.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, M20 4BX, United Kingdom.en
dc.identifier.journalRadiation Researchen
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