Paternal Exposure to Drugs and Environmental Chemicals: Effects on Progeny Outcome

Hales, Barbara F.; Robaire, Bernard

doi:10.1002/j.1939-4640.2001.tb03431.x

Cited by 47 publications

(23 citation statements)

References 110 publications

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“…Previous studies sampled the progeny of exposed parents; therefore, these mutations may be the result of events occurring postfertilization as a consequence of premutational lesions in DNA affecting early cellular divisions (17)(18)(19)(20). Indeed, high levels of somatic mosaicism were found in the outbred SwissWebster mice used, and ESTR loci are known to be highly susceptible to destabilization in early embryogenesis (21)(22)(23).…”

mentioning

confidence: 99%

Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location

Yauk¹,

Polyzos²,

Rowan-Carroll³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

277

202

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Particulate air pollution is widespread, yet we have little understanding of the long-term health implications associated with exposure. We investigated DNA damage, mutation, and methylation in gametes of male mice exposed to particulate air pollution in an industrial/ urban environment. C57BL/CBA mice were exposed in situ to ambient air near two integrated steel mills and a major highway, alongside control mice breathing high-efficiency air particulate (HEPA) filtered ambient air. PCR analysis of an expanded simple tandem repeat (ESTR) locus revealed a 1.6-fold increase in sperm mutation frequency in mice exposed to ambient air for 10 wks, followed by a 6-wk break, compared with HEPA-filtered air, indicating that mutations were induced in spermatogonial stem cells. DNA collected after 3 or 10 wks of exposure did not exhibit increased mutation frequency. Bulky DNA adducts were below the detection threshold in testes samples, suggesting that DNA reactive chemicals do not reach the germ line and cause ESTR mutation. In contrast, DNA strand breaks were elevated at 3 and 10 wks, possibly resulting from oxidative stress arising from exposure to particles and associated airborne pollutants. Sperm DNA was hypermethylated in mice breathing ambient relative to HEPAfiltered air and this change persisted following removal from the environmental exposure. Increased germ-line DNA mutation frequencies may cause population-level changes in genetic composition and disease. Changes in methylation can have widespread repercussions for chromatin structure, gene expression and genome stability. Potential health effects warrant extensive further investigation.DNA adducts ͉ DNA strand breaks ͉ tandem repeat mutation C ombustion of fossil fuels results in the production of complex mixtures of chemicals that are released into the environment and potentially affect millions of people globally. Previous work demonstrated that the offspring of wild birds breeding near integrated steel mills on the North American Great Lakes inherited increased numbers of tandem repeat DNA sequence mutations compared with those from areas without steel mills (1, 2). Subsequent studies investigated expanded simple tandem repeat (ESTR) mutation in outbred laboratory mice caged near two integrated steel mills and a major highway in Hamilton, Ontario, Canada, and at a rural reference site (3, 4). Using a pedigree approach (5), a significant increase in germ-line mutation rate was found in mice housed in the industrial environment compared with the reference site. The majority of mutations were transmitted through the paternal germ line. High-efficiency particulate-air (HEPA) filtration of the ambient air resulted in a significant reduction in mutation frequency, down to levels measured at the reference location (4). Therefore, the particulate fraction of air in this industrial location was largely responsible for the mutagenic hazard.These findings show that chemical pollutants may cause heritable mutation. Further research is required to confirm these results...

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mentioning

confidence: 99%

Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location

Yauk¹,

Polyzos²,

Rowan-Carroll³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

277

202

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show abstract

“…In this scenario, a male is exposed to an environmental toxicant that is absorbed, distributed, biotransformed, and excreted as metabolite or parent compound in seminal fluid. Alternatively, compounds can be adsorbed to sperm and be introduced directly into the egg at fertilization [e.g., cocaine or cyclophosphamide (reviewed in Hales and Robaire 2001;Yazigi et al 1991)]. Any contaminants in semen are transmitted to a woman in the ejaculate.…”

Section: Compounds In Semenmentioning

confidence: 99%

Off to a good start: the influence of pre- and periconceptional exposures, parental fertility, and nutrition on children's health.

Chapin

Robbins

Schieve

et al. 2004

Environ Health Perspect

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The scientific community is developing a compelling body of evidence that shows the importance of the in utero environment (including chemical and hormonal levels) to the ultimate health of the child and even of the aging adult. This article summarizes the evidence that shows this impact begins with conception. Only a full life-cycle evaluation will help us understand these impacts, and only such an understanding will produce logically prioritized mitigation strategies to address the greatest threats first. Clearly, the time for analysis begins when the next generation is but a twinkle in the eye.

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“…Although many chemicals can appear in semen, most will be present at very low levels; the potency of the toxicant, level of exposure, and timing during development all need to be considered. 15,16 1. Male-mediated developmental toxicity may also occur via genetic (gene mutation or chromosomal abnormality), and epigenetic (effect on gene expression, genomic imprinting, or DNA methylation) mechanisms which could cause the fetus to develop abnormally.…”

Section: The Cluster May Have Been Related To Exposures At Tss In Onementioning

confidence: 99%

“…Male-mediated developmental toxicity may also occur via genetic (gene mutation or chromosomal abnormality), and epigenetic (effect on gene expression, genomic imprinting, or DNA methylation) mechanisms which could cause the fetus to develop abnormally. 15,16 Though possible, it is unlikely that such a specific genetic aberration would occur affecting the development of the heart, while allowing other systems to develop correctly and the fetus to survive. However, there is limited suggested evidence of this mechanism in animal studies of malemediated congenital anomalies and exposure to therapeutic drugs and x-rays.…”

Section: The Cluster May Have Been Related To Exposures At Tss In Onementioning

confidence: 99%

Health hazard evaluation report: HETA #99-0343-2882, Thomas Steel Strip Corporation, Warren, Ohio.

2002

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Paternal Exposure to Drugs and Environmental Chemicals: Effects on Progeny Outcome

Cited by 47 publications

References 110 publications

Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location

Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location

Off to a good start: the influence of pre- and periconceptional exposures, parental fertility, and nutrition on children's health.

Health hazard evaluation report: HETA #99-0343-2882, Thomas Steel Strip Corporation, Warren, Ohio.

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