Male-mediated developmental toxicity

Journal Article · Thu Sep 01 00:00:00 EDT 2005 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2005.01.022· OSTI ID:20721952

Anderson, Diana ^[1]

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1. Department of Biomedical Sciences, University of Bradford, Bradford, West Yorkshire, BD7 IDP (United Kingdom)

In recent years, the public has become more aware that exposure of males to certain agents can adversely affect their offspring and cause infertility and cancer. The hazards associated with exposure to ionising radiation have been recognised for nearly a century, but interest was aroused when a cluster of leukaemia cases was identified in young children living in Seascale, close to the nuclear processing plant at Sellafield in West Cumbria. There was a civil court case on behalf of two of the alleged victims of paternal irradiation at Seascale against British Nuclear Fuels. The case foundered on 'the balance of probabilities'. Nevertheless, there was support for paternal exposure from Japanese experimental X-ray studies in mice. The tumours were clearly heritable as shown by F2 transmission. Also, effects of a relatively non-toxic dose of radiation (1Gy) on cell proliferation transmitted to the embryo were manifested in the germ line of adult male mice even after two generations. In addition in humans, smoking fathers appear to give rise to tumours in the F{sub 1} generation. Using rodent models, developmental abnormalities/congenital malformations and tumours can be studied after exposure of males in an extended dominant lethal assay and congenital malformations can be determined which have similar manifestations in humans. The foetuses can also be investigated for skeletal malformations and litters can be allowed to develop to adulthood when tumours, if present, can be observed. Karyotype analysis can be performed on foetuses and adult offspring to determine if induced genetic damage can be transmitted. Using this study design, cyclophosphamide, 1,3-butadiene and urethane have been examined and each compound produced positive responses: cyclophosphamide in all endpoints examined, 1,3-butadiene in some and urethane only produced liver tumours in F{sub 1} male offspring. This suggests the endpoints are determined by independent genetic events. The results from heritable studies with 1,3-butadiene have been used in the parallelogram approach to determine a risk assessment for the germ cells in man.

• OSTI ID: 20721952
• Journal Information: Toxicology and Applied Pharmacology, Vol. 207, Issue 2,suppl.1; Conference: ICT X 2004: 10. international congress of toxicology: Living in a safe chemical world, Tampere (Finland), 11-15 Jul 2004; Other Information: DOI: 10.1016/j.taap.2005.01.022; PII: S0041-008X(05)00228-0; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS
BIOLOGICAL RADIATION EFFECTS
BUTADIENE
CELL PROLIFERATION
CHILDREN
CONGENITAL MALFORMATIONS
ENDOXAN
GERM CELLS
LIVER
MICE
NEOPLASMS
NUCLEAR FUELS
RISK ASSESSMENT
TOXICITY
URETHANE
X RADIATION