Maternal effects and cancer risk in the progeny of mice exposed to X-rays before conception

Dasenbrock, Clemens; Tillmann, Thomas; Ernst, Heinrich; Behnke, Wolfgang; Kellner, Rupert; Hagemann, G; Kaever, Volkhard; Köhler, Manfred; Rittinghausen, Susanne; Möhr, U.; Tomatis, Lorenzo

doi:10.1016/j.etp.2004.12.001

Cited by 19 publications

(12 citation statements)

References 56 publications

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“…However, the result of numerous publications suggests that radiation may also have an indirect effect on genome stability that is transmitted through the germ line of irradiated parents to their offspring (Dubrova 2003, Dasenbrock et al 2005. Due to strong selection against several defects at the earliest stage of pregnancy, this genetic effect of radiation is likely to be difficult to detect in people.…”

Section: Introductionmentioning

confidence: 99%

“…These mutational events may be an indirect effect on genome stability that is transmitted through the germ line of irradiated parents to their offspring (Dubrova 2003, Dasenbrock et al 2005. Teratogenic effects of various types of ionizing radiation at different stages of pregnancy, death, and morphological changes in embryos and fetus of experimental animals have been shown (Hall 2001).…”

Section: Introductionmentioning

confidence: 99%

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Cytogenetic damage in preimplantation mouse embryos generated after paternal and parental γ-irradiation and the influence of vitamin C

Mozdarani

Nazari²

2009

Reproduction

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Cytogenetic damage expressed as micronuclei (MN) in 4-8-cell embryos generated after irradiation of male or male and female mice in the absence and presence of vitamin C was investigated. Male NMRI mice were whole body exposed to 4 Gy g-rays and mated with non-irradiated superovulated female mice in 6 successive weeks after irradiation in a weekly interval. In experiments involving irradiation of both male and female mice, irradiated male mice for 6 weeks post irradiation were mated with female mice irradiated after induction of superovulation. Effect of 100 mg/kg vitamin C (ascorbic acid) on the frequency of MN was also studied. Pregnant animals were euthanized and embryos flushed from the oviducts and fixed on slides. The rate of MN observed in embryos generated from irradiated male compared with control group dramatically increased (P!0.01). Frequency of MN in this group decreased dramatically after vitamin C treatment (P!0.01). Frequency of MN in embryos generated by mating both male and female irradiated mice was higher than that observed for those embryos generated by irradiated male mice alone. However, a considerable modifying effect of vitamin C was observed for this group too (P!0.05). Results indicate that irradiation of gonads during spermatogenesis and preovulatory stage oocytes may lead to unstable chromosomal aberrations and probably stable chromosomal abnormalities affecting pairing and disjunction of chromosomes in successive preimplantation embryos expressed as MN. The way vitamin C reduces clastogenic effects of radiation on germ cells leading to reduced frequency of MN in pre-embryos might be due to its antioxidation and radical scavenging properties.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cytogenetic damage in preimplantation mouse embryos generated after paternal and parental γ-irradiation and the influence of vitamin C

Mozdarani

Nazari²

2009

Reproduction

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“…Early studies of these transgeneration effects used various tests such as the specific locus, dominant lethal, and heritable translocation assays [Generoso et al, 1980;Russell and Kelly, 1982;Green et al, 1987;Russell et al, 1998]. Other studies focused on heritable alterations in cancer incidence and teratogenesis following the parental preconception irradiation [Mohr et al, 1999;Pils et al, 1999;Nomura, 2003;Nomura et al, 2004;Dasenbrock et al, 2005]. In addition to this classic evidence for transmitted effects, it is now apparent that risks to the progeny of irradiated parents also include transgeneration genomic instability [Carls and Schiestl, 1999;Mohr et al, 1999;Barber et al, 2002Shiraishi et al, 2002;Dubrova, 2003a,b;Morgan, 2003b;Niwa, 2003;Nomura, 2003;Nomura et al, 2004;Slovinska et al, 2004;Dasenbrock et al, 2005;Tawn, 2005;Singer et al, 2006].…”

Section: Transgeneration Radiation-induced Effectsmentioning

confidence: 99%

Epigenetic changes and nontargeted radiation effects—Is there a link?

Kovalchuk

Baulch

2008

Environ and Mol Mutagen

125

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It is now well accepted that the effects of ionizing radiation (IR) exposure can be noticed far beyond the borders of the directly irradiated tissue. IR can affect neighboring cells in the proximity, giving rise to a bystander effect. IR effects can also span several generations and influence the progeny of exposed parents, leading to transgeneration effects. Bystander and transgeneration IR effects are linked to the phenomenon of the IR‐induced genome instability that manifests itself as chromosome aberrations, gene mutations, late cell death, and aneuploidy. While the occurrence of the abovementioned phenomena is well documented, the exact mechanisms that lead to their development have still to be delineated. Evidence suggests that the IR‐induced genome instability, bystander, and transgeneration effects may be epigenetically mediated. The epigenetic changes encompass DNA methylation, histone modification, and RNA‐associated silencing. Recent studies demonstrated that IR exposure alters epigenetic parameters in the directly exposed tissues and in the distant bystander tissues. Transgeneration radiation effects were also proposed to be of an epigenetic nature. We will discuss the role of the epigenetic mechanisms in radiation responses, bystander effects, and transgeneration effects. Environ. Mol. Mutagen., 2008. © 2008 Wiley‐Liss, Inc.

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“…The evidence in humans is most derived from case reports and epidemiological studies of consequences to the progeny of paternal occupational exposure to chemicals, ionizing radiation and electromagnetic fields prior to conception (3,(45)(46)(47). Dasenbrock et al (43) indicated that maternal preconceptual X-ray exposure to radiation is associated with a moderately increased incidence of liver and lung tumors in male descendants in C57BL/6N mice. Thus the fact that genetic damage to parental germ cells can be transmitted to the offspring as an origin of carcinogenesis has been well documented, and this was confirmed in the present experiment.…”

Section: ------------------------------------------------------------mentioning

confidence: 99%

“…Tomatis et al (5) subsequently found in the BDV1 rat system that the incidence of nerve tumors was significantly elevated in the F 1 generation when mating occurred two weeks after treatment of 9-week-old male rats with 80 mg/kg of ethylnitrosourea. Dasenbrock et al (43) described that maternal preconceptual exposure in C57BL/6J mice to radiation is associated with a moderately increased incidence of liver and lung tumors in the male descendants. The incidence of total tumors in the F 1 offspring, however, was not different from the control value.…”

Section: ------------------------------------------------------------mentioning

confidence: 99%

Paternal monoenergetic neutron exposure results in abnormal sperm, and embryonal lethality and transgenerational tumorigenesis in mouse F1 offspring

Watanabe

Toyoshima²,

Ishikawa³

et al. 2010

Oncol Rep

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Abstract. Experiments were conducted to assay whether monoenergetic neutron-induced genetic damage in parental germline cells can give rise to development of cancer in the offspring. Seven-week-old C3H male mice were irradiated with monoenergetic neutrons with energy levels of 0.2 or 0.6 MeV at doses of 0, 50, 100 or 200 cGy. Two weeks after irradiation, when the male mice showed an increased incidence of sperm abnormalities, they were mated with virgin 9-week-old C57BL females. Litter size was decreased and embryo lethalities were increased in a dose-dependent manner. Furthermore, tumor incidence in male offspring born to male mice irradiated with 25 or 50 cGy at 0.6 MeV showed a tendency for increase as compared to the non-irradiated group value. Liver tumors in the 50 cGy group were significantly increased (P=0.03). It is concluded that the increased hepatic tumor risk in the F 1 generation may have been caused by genetic transmission of some hepatoma-associated trait(s) induced by monoenergetic neutron irradiation.

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Maternal effects and cancer risk in the progeny of mice exposed to X-rays before conception

Cited by 19 publications

References 56 publications

Cytogenetic damage in preimplantation mouse embryos generated after paternal and parental γ-irradiation and the influence of vitamin C

Cytogenetic damage in preimplantation mouse embryos generated after paternal and parental γ-irradiation and the influence of vitamin C

Epigenetic changes and nontargeted radiation effects—Is there a link?

Paternal monoenergetic neutron exposure results in abnormal sperm, and embryonal lethality and transgenerational tumorigenesis in mouse F1 offspring

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