Female-specific dominant lethal effects in mice

Katoh, Masaya; Cain, K.T.; Hughes, L.A.; Foxworth, L.B.; Bishop, Jack B.; Generoso, W.M.

doi:10.1016/0027-5107(90)90058-c

Cited by 64 publications

(35 citation statements)

References 34 publications

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“…The difference is even higher when the amount of chromosomal damage is considered [49]. Although dictyate oocytes are characterized by a diffuse chromatin state that is thought to make them particularly sensitive to DNA-interacting chemical agents [68][69][70], oocytes have fully functional DNA repair mechanisms throughout oogenesis and provide gene products that are responsible for repairing DNA damage in both parental genomes after fertilization [26,71,72]. Therefore, it is likely that DNA lesions induced by DEB in oocytes are repaired before fertilization and before pronuclear DNA synthesis takes place.…”

Section: Discussionmentioning

confidence: 99%

DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage

Marchetti

Wyrobek

2008

DNA Repair

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The post-meiotic phase of mouse spermatogenesis (spermiogenesis) is very sensitive to the genomic effects of environmental mutagens because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. We hypothesized that repeated exposures to mutagens during this repair-deficient phase result in the accumulation of heritable genomic damage in mouse sperm that leads to chromosomal aberrations in zygotes after fertilization. We used a combination of single or fractionated exposures to diepoxybutane (DEB), a component of tobacco smoke, to investigate how differential DNA repair efficiencies during the three weeks of spermiogenesis affected the accumulation of DEB-induced heritable damage in early spermatids (21-15 days before fertilization, dbf), late spermatids (14-8 dbf) and sperm (7-1 dbf). Analysis of chromosomal aberrations in zygotic metaphases using PAINT/DAPI showed that late spermatids and sperm are unable to repair DEB-induced DNA damage as demonstrated by significant increases (P<0.001) in the frequencies of zygotes with chromosomal aberrations. Comparisons between single and fractionated exposures suggested that the DNA repair-deficient window during late spermiogenesis may be less than two weeks in the mouse and that during this repair-deficient window there is accumulation of DNA damage in sperm.Finally, the dose-response study in sperm indicated a linear response for both single and repeated exposures. These findings show that the differential DNA repair capacity of post-meioitic male germ cells has a major impact on the risk of paternally transmitted heritable damage and suggest that chronic exposures that may occur in the weeks prior to fertilization because of occupational or lifestyle factors (i.e, smoking) can lead to an accumulation of genetic damage in sperm and result in heritable chromosomal aberrations of paternal origin.

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Section: Discussionmentioning

confidence: 99%

DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage

Marchetti

Wyrobek

2008

DNA Repair

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“…These findings are somewhat unexplainable considering cisplatin is widely known to propagate a host of DNA-damaging events, notably chromosomal aberrations occurring in mouse spermatocytes and spermatogonial stem cells. The dose of cisplatin that was administered (10 mg/kg) is perhaps notable in that similar studies employing both the dominant lethal and specific locus tests also failed to display any effect at such a dose (Katoh et al, 1990;Witt & Bishop, 1996). One hypothesis for these negative results is that of potential cell killing inadvertently affecting the amount of mutants available for detection (Barber et al, 2000), owing to the administered dose of cisplatin (10 mg/kg) being twenty times that of the doubling dose for chromosome abnormalities (0.5 mg/kg) (Somers, 2006).…”

Section: Estr Mutation Detection Studiesmentioning

confidence: 99%

The effects of extremely low frequency magnetic fields on mutation induction in mice

Wilson

Haines

Sienkiewicz

et al. 2015

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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“…Special measures must be taken in female dominant lethal tests because early embryonic survival may be affected by chemical-induced changes in female reproductive physiology and because of the limitations on the numbers of litters and offspring obtained from treated females. Nonetheless, it is important that genetic effects be assessed in female germ cells, especially following the recent demonstrations of female-specific germ cell mutagens (30,31).…”

Section: Mouse Assays To Study Germ Cell Mutations Dominant Lethal Testmentioning

confidence: 99%

Fertility, reproduction, and genetic disease: studies on the mutagenic effects of environmental agents on mammalian germ cells.

Shelby

Bishop

Mason

et al. 1993

Environ Health Perspect

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Because geneticaly based diseases have a major inpact on human health, the National Institute of Environmental Health Sciences (NIEHS) has conducted a research and testing program for more than a decade to address chemical induction of heritable genetic damage in the germ cells of mammals. Although most genetic disease results from preexisting mutations, a portion is due to the occurrence ofnew mutations. The supposition that exposure to mutagenic c s contributes to the occurrence of new mutations in the human population is strongly supported by the results from animal models. Such studies clearly demonstrate the potential ofemnironmental chemicals to induce mutations in both somatic and reproductive cells of mammals. This NIEHS program has become a leader in the identification ofgenetic hazards in the environment and in the acquisition of animal model data used by regulatory agencies in assessing genetic risks to human health.

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Female-specific dominant lethal effects in mice

Cited by 64 publications

References 34 publications

DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage

DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage

The effects of extremely low frequency magnetic fields on mutation induction in mice

Fertility, reproduction, and genetic disease: studies on the mutagenic effects of environmental agents on mammalian germ cells.

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