Sidestream tobacco smoke is a male germ cell mutagen

Abstract

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...

Analysis of the Effects of Cigarette Smoke on Staphylococcal Virulence Phenotypes

“…We found that the changes in MRSA induced by cigarette smoke exposure persisted even after the stress was removed, suggesting that cigarette smoke exposure induces heritable changes in MRSA. It has been shown that cigarette smoke and secondhand smoke exposures cause heritable changes in mice and rats (45)(46)(47)(48). The data in humans are less vigorous, but one study demonstrated higher rates of asthma in children and grandchildren of women who smoked during pregnancy (49).…”

Declaring the existence of human germ‐cell mutagens

“…In addition, side-stream cigarette smoke is a germ-cell mutagen in rodents but is negative for cytogenetic damage in mouse bone marrow [Marchetti et al, 2011], indicating that an agent can be negative for cytogenetic damage in somatic cells in vivo but still be a germ-cell mutagen. The mutagenicity of smoking, especially the genotoxic effects of smoking on egg and sperm in humans, makes smoking a likely human germ-cell mutagen [DeMarini, 2004].…”

“…DOI 10.1002/em Table I. b There are two studies, both in mice [Yauk et al, 2007;Marchetti et al, 2011]. These agents induce similar biomarker effects in humans as they do in animals, such as DNA damage in sperm, as reviewed for ionizing radiation and chemotherapy [Kamiguchi and Tateno, 2002], smoking [DeMarini, 2004], and air pollution [Somers, 2011].…”

“…Of 48 agents evaluated for induction of germ-cell mutations in rodents, 39 of them are positive [Shelby 1996;Witt and Bishop, 1996;Russell, 2004;Marchetti and Wyrobek 2005;Glen et al, 2008;Marchetti et al, 2011;Somers, 2011]. The published rodent germ-cell mutagens include ionizing radiation; cancer chemotherapy agents; food components (acrylamide); environmental contaminants (benzo[a]pyrene); and common complex mixtures to which nearly everyone is exposed, such as main-and side-stream tobacco smoke, diesel exhaust, and the particulate fraction of air pollution [Yauk et al, 2007;Marchetti et al, 2011;Ritz et al, 2011;Somers, 2011]. Table I illustrates that some of these agents are carcinogenic and somatic-cell mutagens in both humans and rodents, as well as germ-cell mutagens in rodents.…”

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

“…Such sensitivity of ESTR loci signified a potential useful tool for studies of environmental pollution thus, lastly but of equal importance, is their implementation in the analysis of (d) environmental mutagens, including ambient urban/industrial air pollution (Somers et al, 2002(Somers et al, , 2004Yauk et al, 2008;Zhou et al, 2009), diesel exhaust particles (Ritz et al, 2011) and sidestream tobacco smoke (Yauk et al, 2007;Marchetti et al, 2011). A similar detection of de novo mutations in ESTRs has also been observed in vitro, signifying a correlation between the mutation responses of cultured embryonic fibroblasts and germ cells and somatic cells in vivo following treatment with chemical mutagens (Polyzos et al, 2006a(Polyzos et al, , 2006b).…”