Hereditary Minisatellite Mutations among the Offspring of Estonian Chernobyl Cleanup Workers

Kiuru, Anne; Auvinen, Anssi; Luokkamäki, Mikko; Makkonen, Kaisa; Veidebaum, Toomas; Tekkel, Mare; Rahu, Mati; Hakulinen, Timo; Servomaa, Kristina; Rytömaa, T.; Mustonen, R

doi:10.1667/0033-7587(2003)159[0651:hmmato]2.0.co;2

Cited by 48 publications

(41 citation statements)

References 22 publications

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“…In addition, a number of studies have failed to detect an increase in mutations among the children of Chernobyl cleanup workers (34)(35)(36)(37). This may be caused largely by the lack of useful tools and approaches to evaluate the potential for agents to produce heritable effects.…”

Section: Resultsmentioning

confidence: 99%

Sidestream tobacco smoke is a male germ cell mutagen

Marchetti

Rowan-Carroll

Williams

et al. 2011

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

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Active cigarette smoking increases oxidative damage, DNA adducts, DNA strand breaks, chromosomal aberrations, and heritable mutations in sperm. However, little is known regarding the effects of second-hand smoke on the male germ line. We show here that short-term exposure to mainstream tobacco smoke or sidestream tobacco smoke (STS), the main component of secondhand smoke, induces mutations at an expanded simple tandem repeat locus (Ms6-hm) in mouse sperm. We further show that the response to STS is not linear and that, for both mainstream tobacco smoke and STS, doses that induced significant increases in expanded simple tandem repeat mutations in sperm did not increase the frequencies of micronucleated reticulocytes and erythrocytes in the bone marrow and blood of exposed mice. These data show that passive exposure to cigarette smoke can cause tandem repeat mutations in sperm under conditions that may not induce genetic damage in somatic cells. Although the relationship between noncoding tandem repeat instability and mutations in functional regions of the genome is unclear, our data suggest that paternal exposure to second-hand smoke may have reproductive consequences that go beyond the passive smoker.DNA mutation | micronuclei | germline | spermatogenesis D espite years of intense public campaigns to limit and reduce tobacco consumption, smoking is still widespread, and its health effects remain a significant public concern. Approximately 35% of men of reproductive age in the United States smoke cigarettes (1), and there is extensive evidence to suggest that tobacco smoking can result in abnormal reproductive outcomes such as spontaneous abortions and birth defects (2). Men who smoke are at high risk for several semen abnormalities, including reduced motility, sperm DNA damage such as DNA breaks and adducts, and chromosomal abnormalities (3). In mice, exposure to mainstream tobacco smoke (MTS) induces germ-line mutations in expanded simple tandem repeats (ESTR) that can be transmitted to the progeny, causing irreversible modifications in the genome of the offspring (4). Recently, the International Agency for Research on Cancer concluded that there is enough evidence to link paternal smoking in humans with increased risk of childhood cancer, suggesting that tobacco smoking causes heritable germ cell mutation in humans (5).Exposure to second-hand smoke also remains widespread, with an estimated 40% of nonsmokers being exposed to secondhand smoke (6). Much less is known about the health effects of second-hand (or passive) smoking, although evidence is rapidly accumulating that exposure to second-hand smoke can be as harmful and hazardous to human health as active smoking (6, 7), and that there may be no risk-free level of exposure (8). Sidestream tobacco smoke (STS), the main component of secondhand smoke, is a complex mixture of more than 4,000 chemicals, including at least 50 known carcinogens (8). Qualitative differences between MTS-the smoke inhaled by active smokers-and STS are small; however, some toxicants...

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Section: Resultsmentioning

confidence: 99%

Sidestream tobacco smoke is a male germ cell mutagen

Marchetti

Rowan-Carroll

Williams

et al. 2011

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

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“…Based on these observations, a radiosensitive window was proposed in which certain stages of the spermatogenesis are sensitive to low-dose and low dose-rate radiations for the induction of minisatellite mutation. Another study on the children of Estonian clean-up workers suggested a slight but nonsignificant elevation of the mutation frequency only when the dose to the fathers was above 0.2 Sv (Kiuru et al, 2003).…”

Section: Radiation Induction Of Minisatellite Instability In Humans: mentioning

confidence: 96%

Induced genomic instability in irradiated germ cells and in the offspring; reconciling discrepancies among the human and animal studies

Niwa

2003

Oncogene

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Many studies confirmed that radiation induces genomic instability in whole-body systems. However, the results of the studies are not always consistent with each other. Attempts are made in the present review to resolve the discrepancies. Many of the studies in human and experimental animals utilize the length change mutation of minisatellite sequences as a marker of genomic instability. Minisatellite sequences frequently change their length, and the data obtained by conventional Southern blotting give rather qualitative information, which is sometimes difficult to scrutinize quantitatively. This is the problem inevitably associated with the study of minisatellite mutations and the source of some conflicts among studies in humans and mice. Radiation induction of genomic instability has also been assessed in whole-body experimental systems, using other markers such as the mouse pink-eyed unstable allele and the specific pigmentation loci of medaka fish (Oryzias latipes). Even though there are some contradictions, all these studies have demonstrated that genomic instability is induced in the germ cells of irradiated parents, especially of males, and in offspring born to them. Among these, transmission of genomic instability to the second generation of irradiated parents is limited to the mouse minisatellite system, and awaits further clarification in other experimental systems.

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“…Although extensively researched in humans (Jeffreys et al, 1985bJeffreys, 1987), DNA fingerprint analysis has shown that they are omnipresent throughout the genome of most organisms and higher eukaryotes (Burke & Bruford, 1987;Jeffreys et al, 1987;Gilbert et al, 1990;Andersen & Nilsson-Tillgren, 1997;Bois et al, 1998a). Shown to exhibit high levels of germline mutation rates (up to 15% per gamete) (Vergnaud et al, 1991), minisatellites have thus been successfully utilised as a tool for monitoring DNA mutation following exposure to environmental doses of mutagenic agents in both human (Dubrova et al, 1996(Dubrova et al, , 1997Kodaira et al, 1995Kodaira et al, , 2004Satoh et al, 1996;Livshits et al, 2001;Kiuru et al, 2003), and animal populations (Yauk & Quinn, 1996;Yauk et al, 2000).…”

Section: Minisatellitesmentioning

confidence: 99%