This report reviews the literature on the genotoxicity of mainstream tobacco smoke and cigarette smoke condensate (CSC) published since 1985. CSC is genotoxic in nearly all systems in which it has been tested, with the base/neutral fractions being the most mutagenic. In rodents, cigarette smoke induces sister chromatid exchanges (SCEs) and micronuclei in bone marrow and lung cells. In humans, newborns of smoking mothers have elevated frequencies of HPRT mutants, translocations, and DNA strand breaks. Sperm of smokers have elevated frequencies of aneuploidy, DNA adducts, strand breaks, and oxidative damage. Smoking also produces mutagenic cervical mucus, micronuclei in cervical epithelial cells, and genotoxic amniotic fluid. These data suggest that tobacco smoke may be a human germ-cell mutagen. Tobacco smoke produces mutagenic urine, and it is a human somatic-cell mutagen, producing HPRT mutations, SCEs, microsatellite instability, and DNA damage in a variety of tissues. Of the 11 organ sites at which smoking causes cancer in humans, smoking-associated genotoxic effects have been found in all eight that have been examined thus far: oral/nasal, esophagus, pharynx/larynx, lung, pancreas, myeoloid organs, bladder/ureter, uterine cervix. Lung tumors of smokers contain a high frequency and unique spectrum of TP53 and KRAS mutations, reflective of the PAH (and possibly other) compounds in the smoke. Further studies are needed to clarify the modulation of the genotoxicity of tobacco smoke by various genetic polymorphisms. These data support a model of tobacco smoke carcinogenesis in which the components of tobacco smoke induce mutations that accumulate in a field of tissue that, through selection, drive the carcinogenic process. Most of the data reviewed here are from studies of human smokers. Thus, their relevance to humans cannot be denied, and their explanatory powers not easily dismissed. Tobacco smoke is now the most extreme example of a systemic human mutagen.

Genotoxicity of tobacco smoke and tobacco smoke condensate: a review.

This report reviews the literature on the genotoxicity of mainstream tobacco smoke and cigarette smoke condensate (CSC) published since 1985 CSC is genotoxic in nearly all systems in which it has been tested, with the base/neutral fractions being the most mutagenic In rodents, cigarette smoke induces sister chromatid exchanges (SCEs) and micronuclei in bone marrow and lung cells In humans, newborns of smoking mothers have elevated frequencies of HPRT mutants, translocations, and DNA strand breaks Sperm of smokers have elevated frequencies of aneuploidy, DNA adducts, strand breaks, and oxidative damage Smoking also produces mutagenic cervical mucus, micronuclei in cervical epithelial cells, and genotoxic amniotic fluid These data suggest that tobacco smoke may be a human germ-cell mutagen Tobacco smoke produces mutagenic urine, and it is a human somatic-cell mutagen, producing HPRT mutations, SCEs, microsatellite instability, and DNA damage in a variety of tissues Of the 11 organ sites at which smoking causes cancer in humans, smoking-associated genotoxic effects have been found in all eight that have been examined thus far: oral/nasal, esophagus, pharynx/larynx, lung, pancreas, myeoloid organs, bladder/ ureter, uterine cervix Lung tumors of smokers contain a high frequency and unique spectrum of TP53 and KRAS mutations, reflective of the PAH (and possibly other) compounds in the smoke Further studies are needed to clarify the modulation of the genotoxicity of tobacco smoke by various genetic polymorphisms These data support a model of tobacco smoke carcinogenesis in which the components of tobacco smoke induce mutations that accumulate in a field of tissue that, through selection, drive the carcinogenic process Most of the data reviewed here are from studies of human smokers Thus, their relevance to humans cannot be denied, and their explanatory powers not easily dismissed Tobacco smoke is now the most extreme example of a systemic human mutagen

Genotoxicity of tobacco smoke and tobacco smoke condensate

The goal of the current study was to conduct mutagenicity testing of the urine and serum samples obtained from rats implanted with either DU or tantalum pellets using the Ames reversion assay. We wanted to determine if there was a timeor metal dose-dependent relationship to urine mutagenicity. Additionally, we wanted to evaluate the relationship between urine uranium levels and mutagenic potential. The data strongly indicate that urine mutagenicity is correlated with increased urine uranium content. The implications of these results to the development of a monitoring program designed to assess the health effects of chronic exposure to internalized DU in humans is discussed.

Urinary and serum mutagenicity studies with rats implanted with depleted uranium or tantalum pellets

Monitoring exposure of nursing and pharmacy personnel to cytotoxic drugs: urinary mutation assays and urinary platinum as markers of absorption

An extended follow up of 1221 chromium and nickel exposed welders in the Federal Republic of Germany confirmed an increased relative risk of 1.6 for all cancers compared with an internal reference group of 1694 turners. In an external comparison an excess of deaths from malignant tumours compared with that expected from the national mortality rates was found (standardised mortality ratio (SMR) = 109), which was clearly related to both time since first exposure and duration of exposure. Mortality from lung cancer was increased among welders (SMR = 113) but also among turners (SMR = 108). The difference remained when the subgroups were compared according to smoking information. A large excess of mesothelioma as a cause of death could be attributed to exposure to asbestos. The significantly increased SMR seen for urogenital tumours and "other or unspecified tumours" showed, however, an inverse relation with time since first exposure. This and other inconsistencies in the analysis by type of welding do not permit conclusive statements. Thus a further extension of follow up seems warranted.

https://oem.bmj.com/content/oemed/48/10/675.full.pdf

Risk of cancer for arc welders in the Federal Republic of Germany: results of a second follow up (1983-8).

Urine samples from a control population and from a population of chemical workers from two chemical plants near Florence, Italy, were analyzed for the presence of mutagenic chemicals by the Salmonella/microsome test. When tested with strain TA 1538, the urine of nonsmoking chemical workers showed higher mutagenic activity than that of controls in the presence of in vitro metabolic activation, but no difference was found between controls and chemical workers who both smoked. Increased mutagenic activity was observed in the group of control smokers compared to control nonsmokers, but the same effect was not observed for chemical workers. When TA 100 was used as the tester strain, the chemical workers, both smoking and nonsmoking, had significantly higher mutagenic activity than controls. The mutagenic activity fell to control levels in some workers’ urine after 20 d leave. Although some perturbing effects of smoking habits were observed, the results seemed to indicate the usefulness of the Salmonella/ micro...

Vanni Vannucci

Papers

Exposure to carcinogenic chemicals and smoking increases urinary excretion of mutagens in humans.