1,3-Butadiene has been assessed as a Priority Substance under the Canadian Environmental Protection Act. The general population in Canada is exposed to 1,3-butadiene primarily through ambient air. Inhaled 1,3-butadiene is carcinogenic in both mice and rats, inducing tumors at multiple sites at all concentrations tested in all identified studies. In addition, 1,3-butadiene is genotoxic in both somatic and germ cells of rodents. It also induces adverse effects in the reproductive organs of female mice at relatively low concentrations. The greater sensitivity in mice than in rats to induction of these effects by 1,3-butadiene is likely related to species differences in metabolism to active epoxide metabolites. Exposure to 1,3-butadiene in the occupational environment has been associated with the induction of leukemia; there is also some limited evidence that 1,3-butadiene is genotoxic in exposed workers. Therefore, in view of the weight of evidence of available epidemiological and toxicological data, 1,3-butadiene is considered highly likely to be carcinogenic, and likely to be genotoxic, in humans. Estimates of the potency of butadiene to induce cancer have been derived on the basis of both epidemiological investigation and bioassays in mice and rats. Potencies to induce ovarian effects have been estimated on the basis of studies in mice. Uncertainties have been delineated, and, while there are clear species differences in metabolism, estimates of potency to induce effects are considered justifiably conservative in view of the likely variability in metabolism across the population related to genetic polymorphism for enzymes for the critical metabolic pathway.
Results of a population and cytogenetic survey conducted on groups of adolescents from ecologically different parts of Kemerovskaya oblast, a large industrialized area in Western Siberia, are presented. Significant inter-group variations in the frequencies of spontaneous chromosomal aberrations were detected. In adolescents from the small miners' towns of Tashtagol and Myski, located in the southern part of the region, the highest frequencies of chromosome aberrations were revealed (5.87 +/- 0.62% and 6.72 +/- 0.54%, respectively). The peculiarities of the qualitative spectrum of cytogenetic defects observed suggested that the populations studied were exposed to radiation. The mean frequency of chromosome aberrations in groups of adolescents from Kemerovo, a large center of chemical industry, was equal to 3.49 +/- 0.44%, which is an additional evidence of mutagenic exposure. Chromosomal mutagenesis in this case is thought to be induced mainly by chemical genotoxic agents. However, the mutagenic effects of low doses of radiation cannot be excluded.
Considerable variations in the frequency of spontaneous chromosomal aberrations were revealed during a cytogenetic study of two groups of adolescents from ecologically different areas of Kemerovskaya oblast'. In a sample of adolescents living in an industrial center (the Kemerovo city), this parameter (1.4 +/- 0.37%) did not exceed the population average value, whereas adolescents of the same age from a mountain region with sparse industry (the town of Tashtagol) exhibited, on average, a frequency of 5.87 +/- 0.62%. An increased proportion of chromosomal-type aberrations in the qualitative spectrum of cytogenetic damage, which was observed for the group of adolescents from Tashtagol, suggests that this population was exposed to radiation.
Early discussion regarding smoke produced by both surgical lasers and electrosurgical machines concluded that the smoke produced by these instruments was little more than a malodorous nuisance. Animal and human studies to date, however, have suggested that this smoke is, indeed, dangerous. This smoke has been shown to be mutagenic and can contain bacteria and viruses, the HIV virus being the most notable. Furthermore, these particles are small enough to penetrate deep within the respiratory tract. In response to the concerns raised by these hazards, commercial smoke evacuation systems have been designed to greatly reduce the number of hazardous particles, as well as the noxious odor produced by electrosurgery and laser surgery. The efficacy of these systems, however, is dependent o n usage and placement close to the surgical site. This review paper presents the potential hazards of electrosurgical smoke, along with some guidelines on how to properly protect hospital staff and patients from these hazards.
Contaminated soil is a serious environmental problem, constituting a risk to humans and the environment. Polycyclic aromatic hydrocarbons (PAHs) are often present at contaminated sites. However, risk levels are difficult to estimate because of the complexity of contaminants present. Here, we compare cellular effects of extracts from contaminated soils collected at six industrial settings in Sweden. Chemical analysis showed that all soils contained complex mixtures of PAHs and oxy-PAHs. Western blotting and immunocytochemistry were used to investigate DNA damage signaling in HepG2 cells exposed to extracts from these soils. The effects on phosphorylated Mdm2, p53, Erk, H2AX, 53BP1, and Chk2, cell cycle regulating proteins (cyclin D1 and p21), and cell proliferation were compared. We found that most soil extracts induced phosphorylation of Mdm2 at the 2A10 epitope at low concentrations. This is in line with previous studies suggesting that this endpoint reflects readily repaired DNA-damage. However, we found concentration- and time-dependent gammaH2AX and 53BP1 responses that were sustained for 48 hr. These endpoints may reflect the presence of different types of persistent DNA-damage. High concentrations of soil extracts decreased cyclin D1 and increased p21 response, indicating cell cycle arrest. Phosphorylation of Mdm2 at Ser166, which attenuates the p53 response and is induced by many tumor promoters, was induced in a time-dependent manner and was associated with Erk phosphorylation. Taken together, the PAH extracts elicited unpredictable signaling responses that differed between samples. More polar compounds, i.e., oxy-PAHs, also contributed to the complexity.
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant mutagenic heterocyclic amine (HCA) present in cooked foods. PhIP induces colon cancer in male Fischer 344 (F344) rats, and its role in human colon carcinogenesis has been suspected. To study the ecogenetics in PhIP colon carcinogenesis, rat system using aberrant crypt focus (ACF) formation as a phenotypic marker was applied. Among Buffalo (BUF), Brown Norway (BN), F344 and ACI/N (ACI) strains of rats, F344 rats produced a lower level of PhIP-DNA adducts than other three strains, and the number of ACFs/rat was highest in BUF, intermediate in BN and F344 and lowest in ACI. Thus there was no correlation between adduct levels and number of ACF induced by PhIP. F1 progenies of BUF and ACI developed ACF at a similar level to that of F344, and F1 progenies of F344 and ACI developed ACF at a similar level to that of F344. Thus it was indicated that susceptibility of F344 to the ACF induction was autosomally dominant over ACI rats. The results also suggest that BUF rats have at least two genes, one is autosomally recessive against ACI rats and one is autosomally dominant similar to that F344 has. A total of 170 progeny of ACI backcross of F344/ACI F1 were examined for number of ACFs and 65 progeny were phenotyped as F344 and 60 were ACI. Using these 125 rats, chromosomal mapping is being performed using markers of simple sequence length polymorphism (SSLP) and representational difference analysis (RDA). By mapping the gene, we will be able to identify humans who might belong to high risk group in general population, and cancer can be prevented more efficiently by attaining early diagnosis.
Genetic studies in environmental hygiene have been conducted in Russia since approximately 1965 and chiefly represented by those performed at the A. N. Sysin Research Institute of Human Ecology and Environment Hygiene in three areas: evaluation of the mutagenic activity of individual chemical compounds; identification of the summary mutagenic activity of chemical pollutants in the environmental objects; and that of mutagenic factors during examination of a population. At present, a system harmonized with international approaches has been elaborated to evaluate the genetic safety of various environmental factors; a methodology has been developed to evaluate the organ specificity of enotoxic activity of chemical compounds; a highly informative karyological analysis of different cells and tissues has been put into practice. The Institute has initiated wide investigations to assess individual genetic predisposition or resistance of human beings to environmental factors and to the development of pathological conditions, multifactorial diseases. Problems of genetic studies in hygiene are defined and prospects for further development outlined.