Maternal exposure to environmental tobacco smoke,GSTM1/T1 polymorphisms and oxidative stress

Environmental tobacco smoking (ETS) is known to be associated with adverse pregnancy outcomes. The purpose of this study was to investigate the relationship between maternal exposure to ETS and oxidative stress for neonates, as well as the effect of maternal genetic polymorphisms, glutathione-S-transferase M1 (GSTM1) and GSTT1, on this relationship.We used the radioimmunoassay to measure the urinary concentration of cotinine in 266 pregnant women who denied smoking cigarettes during pregnancy and in their singleton babies. In addition, the urinary concentration of malondialdehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OH-dG) were assessed using high-performance liquid chromatography and enzyme-linked immunosorbent assay, respectively. We also extracted DNA from whole blood obtained from the mothers and then conducted polymerase chain reaction on the samples to determine the GSTM1 and GSTT1 genotypes.The maternal cotinine concentration was found to be significantly associated with the fetal cotinine concentration, particularly for mothers whose urine cotinine concentrations were above 120 μg/g cr (p < 0.01). The fetal urine cotinine concentration was also found to be significantly associated with the fetal urine MDA concentration (p < 0.01). When the null type maternal GSTM1 or the wild type GSTT1 was present, the maternal oxidative stress level increased significantly as the maternal continine concentration increased (MDA: p < 0.01; 8-OH-dG: p < 0.01). No significant relationships were found between maternal cotinine and fetal oxidative stress markers, however, the fetal MDA levels increased significantly as fetal cotinine levels increased.These results suggest that the maternal exposure to ETS affects the fetal urine cotinine concentration and induces production of maternal oxidative stress. In addition, maternal genetic polymorphisms of GSTM1 and GSTT1 may modify the oxidative stress by maternal exposure to ETS.     

Genetic susceptibility of term pregnant women to oxidative damage

Genetic polymorphisms involved in the activation and detoxification of exogenous chemicals and in the production and scavenging of reactive oxygen species may modulate the levels of oxidative injury biomarker. We investigated 81 pregnant women in Inchon, Korea. In addition to a questionnaire survey, urinary concentrations of 8-hydroxydeoxyguanosine (8-OH-dG) and malondialdehyde (MDA) were measured as oxidative injury biomarkers. Cytochrome P-450(CYP)1A1, CYP2E1, glutathione S-transferase (GST)M1 and GSTT1 polymorphisms and myeloperoxidase (MPO) and manganese superoxide dismutase (MnSOD) polymorphisms were evaluated to determine the effect of genetic modification on urinary 8-OH-dG and MDA. The concentrations of urinary 8-OH-dG were significantly elevated in the presence of the MnSOD variant genotype (P=0.04) and in the case of GSTM1 null status (P=0.02) by multivariate regression. The concentrations of urinary MDA were not affected significantly by the genetic polymorphisms. This result shows that oxidative stress injury is modified by some heritable polymorphisms, including GSTM1 and MnSOD.     

Oxidative stress in pregnant women and birth weight reduction

The purpose of this study is to evaluate the role of maternal oxidative stress in lowering neonatal birth weight. Women (N = 261) with singleton pregnancy were analyzed for biomarker levels of oxidative stress after recruitment at the time of hospitalization for delivery in Korea between 2000 and 2001. Among the neonates, 247 births were full-term infants and 14 births were pre-term infants. Biomarkers measured for oxidative stress were maternal urinary 8-hydroxydeoxyguanosine (8-OH-dG) and malondialdehyde (MDA). The women with pre-term infants had higher concentrations of urinary 8-OH-dG and MDA than those with full-term babies. The concentrations of maternal urinary 8-OH-dG and MDA were inversely associated with birth weight of full-term deliveries after adjusting for potential confounders including maternal age, body mass index, dietary intake, alcohol consumption, smoking exposure, occupational status, and neonatal sex (P < 0.05). This study demonstrates that increase of 8-OH-dG and MDA concentrations in urine of pregnant women were associated with reduced birth weight in full-term deliveries.     

Variations in urinary 1-hydroxypyrene glucuronide in relation to smoking and the modification effects of GSTM1 and GSTT1.

The measurement of the pyrene metabolite, 1-hydroxypyrene, in human urine has been used to assess recent exposure to polycyclic aromatic hydrocarbons (PAH). The objective of this study was to see whether genetic polymorphisms in metabolic enzymes could explain some of the variation in urinary 1-hydroxypyrene glucuronide (1-OHPG) excretion in relation to smoking. Forty-seven male hospital workers, who were not occupationally exposed to PAH, participated in this study. The urine samples were analyzed for 1-OHPG utilizing immunoaffinity chromatography and synchronous fluorescence spectroscopy. The analysis of GSTM1 and GSTT1 polymorphism was performed by PCR. The 1-OHPG concentration in the urine of the hospital workers was 0.57 +/- 0.85 micromol/mol creatinine, and ranged from 0.02 to 5.04 mciromol/mol creatinine. Cigarette smoking was significantly correlated with urinary 1-OHPG (r = 0.3976, P = 0.0056). The 1-OHPG excretion in GSTM1-deficient smokers was higher than that in GSTM1-positive smokers. On the other hand, 1-OHPG excretion was higher in GSTT1-positive smokers than in GSTT1-deficient smokers. It is important to note the variability of individual PAH metabolite excretion due to different GSTM1 and GSTT1 genotypes.     

Influence of GSTT1 and GSTM1 genotypes on sunburn sensitivity

Background: Exposure to sunlight may cause sunburn, skin cancer or phototoxic reactions to certain drugs such as Hypericum extract. All these are ultraviolet B (UVB)-mediated reactions which may be modulated by individual genetic susceptibility. UVB exposure results in oxidative stress. Many products of oxidative stress are detoxified by glutathione-S-transferases mu 1 (GSTM1) and theta 1 (GSTT1). Deletion polymorphisms (genotype *0/*0) of GSTM1 and GSTT1 occur in 50% and 20% of Caucasians, respectively. By affecting the individual ability to detoxify oxidative stress-related products, they may influence the severity of the cutaneous photoreaction. Methods: Minimal erythema doses (MED) of UVB irradiation on the skin were determined in 110 subjects who were selected according to their GSTT1 genotype (28 GSTT1*0/*0, 54 GSTT1*A/*0, and 28 GSTT1*A/*A). Genotypes were detected with novel polymerase chain reaction (PCR) assays that allow the differentiation between homozygous and heterozygous GSTT1 and GSTM1 deletions. Results: In the absence of GSTT1 enzyme, the susceptibility of individuals to UVB-induced inflammatory skin reactions increased significantly (p = 0.02, ANCOVA). ‘Gene-equivalents’ were calculated from the number of functional GSTM1 and GSTT1 alleles as a measure of the gene-dose. UVB sensitivity correlated with gene dose up to a threshold above which additional GSTT1 or GSTM1 alleles did not provide additional protection. Volunteers who were homozygously deficient in GSTT1 and GSTM1 were most sensitive to UVB. Interestingly, individuals with high GSTM1 gene-doses showed increased photosensitization after administration of Hypericum extract (St. John’s wort). Conclusion: Individuals harboring the *0/*0 genotype of GSTT1 and/or GSTM1 showed enhanced UVB-induced cutaneous damage. Moreover, GST genotypes modulated Hypericum-induced photosensitization.     

Polymorphism in CYP1A1, GSTMI, GSTT1 genes and organochlorine pesticides in the etiology of hypospadias

Exposure to endocrine-disrupting chemicals (EDCs) and maternal endogenous estrogen may cause hypospadias, common congenital anomaly. Several organochlorine pesticides (OCPs) have been reported to possess an endocrine-disrupting potential. Cytochrome P4501A1 (CYP1A1) and glutathione S-transferases (GSTM1 and GSTT1) of xenobiotic metabolizing enzyme family are involved in the metabolism of various environmental toxicants and steroidal hormones. Hence, the present study was designed to evaluate the role of CYP1A1, GSTM1, GSTT1 genes polymorphism, OCPs levels and risk of hypospadias. A total of 80 hypospadiac and 120 age-matched control boys were included. OCP levels in blood were determined using Gas Chromatograph equipped with electron capture detector (GC-ECD) and polymorphism in CYP1A1, GSTM1 and GSTT1 genes was evaluated by RFLP and multiplex PCR method. We observed significant high levels of β-hexachlorohexane (HCH), γ-HCH, and p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE) in the cases. CYP1A1 polymorphisms were not significantly different among cases and controls, whereas concomitant deletion of GSTM1 and GSTT1 genotypes was significantly higher in cases as compared to controls. However, after adjusting for low birth weight and maternal occupational exposure, the results did not remain significant but odds of risk was higher (OR = 1.72, p = 0.14) among cases. In conclusion, our study suggests irrespective of genetic predisposition, higher level of some OCPs may be associated with increased risk of hypospadias.     

Genetic polymorphism of glutathione S-transferase M1 and T1 in Delhi population of Northern India

Glutathione S-transferases (GSTs), protect cells from reactive chemical intermediates and oxidative stress. Among different classes of GSTs, GSTM1 (Mu) and GSTT1 (theta) are found to be genetically deleted. Present study was intended to genotype homozygous null distribution of GSTM1 and GSTT1 in healthy individuals of Delhi, located in Northern India. Out of 309 healthy individuals included in this study, we have found genetic deletion in 21% and 27.4%, GSTM1 and GSTT1 genes, respectively. A small proportion (0.7%) population showed deletion of both the genes. The prevalence of the GSTM1(*)0/0 and GSTT1(*)0/0 genotypes varied within India compared to communities in Chinese, Japanese, Korean and Caucasian.     

Association between glutathione S-transferase A1, M1 and T1 polymorphisms and hypertension

The importance of oxidative stress in hypertension has recently received increasing attention. The association between the incidence of hypertension and a super family of antioxidant enzymes, glutathione S-transferase (GST)A1, GSTM1 and GSTT1, polymorphisms was investigated in 468 Japanese participants in a health screening program. The frequency of the GSTA1*B allele carriers was significantly higher in hypertensive patients than normotensive participants [adjusted odds ratio (OR): 1.8; 95% confidence interval (CI): 1.1-2.9]. The risk of hypertension was significantly increased in the GSTA1*B allele carriers having also the GSTM1 null genotype or both the GSTM1 and GSTT1 null genotypes (adjusted OR: 2.4; 95% CI: 1.2-4.9; adjusted OR: 3.1; 95% CI: 1.0-9.5, respectively). This is the first report identifying the GSTA1*B allele as a genetic risk factor for hypertension. The determination of the GST genotypes may help in identifying individuals at high-risk for hypertension.     

Modulation of the GSTT1 activity by the GSTM1 phenotype in a sample of Italian farm-workers

Glutathione S-transferase (GST) isozymes catalyze nucleophilic attack by reduced Glutathione (GSH) on a variety of electrophilic compounds and play a central role in biotransformation of xenobiotics (Hayes et al., Annu Rev Pharmacol Toxicol 45:51–88, 2005). We performed a case–control study to evaluate the GSTM1 and GSTT1 polymorphisms and to investigate if exposure to pesticides conditions the GSTT1 activity level in 115 healthy controls and 90 farm-workers exposed to pesticides. Polymorphisms were investigated using a GSTM1 or a GSTT1-specific PCR. Enzyme activity was measured by means of DCM as co-substrate, as described by Bruhn et al. (Biochem Pharmacol 56:1189–1193, 1998). There was no significant difference between the farm-workers and the healthy controls regarding the distribution of various alleles of the GSTM1 and GSTT1 genes and the GSTT1 enzyme activity. In farm-workers, the GSTM1 null genotype was associated with a significant increase of GSTT1 activity, suggesting a regulative mechanism common to GSTM1 and GSTT1 enzymes after exposure to xenobiotics.     

Biomarkers of oxidative stress and DNA damage in agricultural workers: a pilot study

Oxidative stress and DNA damage have been proposed as mechanisms linking pesticide exposure to health effects such as cancer and neurological diseases. A study of pesticide applicators and farmworkers was conducted to examine the relationship between organophosphate pesticide exposure and biomarkers of oxidative stress and DNA damage. Urine samples were analyzed for OP metabolites and 8-hydroxy-2'-deoxyguanosine (8-OH-dG). Lymphocytes were analyzed for oxidative DNA repair activity and DNA damage (Comet assay), and serum was analyzed for lipid peroxides (i.e., malondialdehyde, MDA). Cellular damage in agricultural workers was validated using lymphocyte cell cultures. Urinary OP metabolites were significantly higher in farmworkers and applicators (p<0.001) when compared to controls. 8-OH-dG levels were 8.5 times and 2.3 times higher in farmworkers or applicators (respectively) than in controls. Serum MDA levels were 4.9 times and 24 times higher in farmworkers or applicators (respectively) than in controls. DNA damage (Comet assay) and oxidative DNA repair were significantly greater in lymphocytes from applicators and farmworkers when compared with controls. Markers of oxidative stress (i.e., increased reactive oxygen species and reduced glutathione levels) and DNA damage were also observed in lymphocyte cell cultures treated with an OP. The findings from these in vivo and in vitro studies indicate that organophosphate pesticides induce oxidative stress and DNA damage in agricultural workers. These biomarkers may be useful for increasing our understanding of the link between pesticides and a number of health effects.     

Offspring sex ratio is not associated with parental GSTT1 and GSTM1 null genotypes

The present study evaluated the association between offspring sex ratio and parental inherited variations of xenobiotic metabolism by glutathione S-transferase (GST) T1 and GSTM1. Polymorphisms of GSTT1 and GSTM1 were investigated in 235 Iranian Muslims (153 males, 82 females) using polymerase chain reaction-based method. Statistical analysis of 890 offspring in the study families revealed that there was no association between GSTM1 null genotype of either the fathers (OR=1.28; 95% CI=0.88-1.85; P=0.17) or mothers (OR=0.77; 95% CI=0.49-1.19; P=0.22) and offspring sex ratio. There was no association between paternal GSTT1 null genotype and sex ratio in offspring (OR=1.04; 95% CI=0.71-1.54; P=0.84), whereas there was a weak association between maternal GSTT1 null genotype and offspring sex ratio (OR=1.54; 95% CI=1.0-2.38; P=0.05). Combination of parental GSTT1 and GSTM1 genotypes showed no association with offspring sex ratio.     

Glutathione S-transferase GSTM1 and GSTT1 null genotypes as potential risk factors for urothelial cancer of the bladder

 Onehundred-and-thirteen patients with cancer of the urinary bladder (cases) were examined with respect to the frequency of null genotypes of the polymorphic glutathione S-transferases GSTM1 and GSTT1. The allelic background in the German population of the area was evaluated by analysing 170 newborns (controls). The frequency of GSTM1 and GSTT1 null genotypes in this population, using methods based upon internal standard controlled polymerase chain reaction (PCR), was 0.54 and 0.18 respectively. An elevated relative bladder cancer risk of GSTM1 null genotype carriers was indicated by comparison of this background with the data of the bladder cancer cases (OR = 1.81; 95% CI [1.10, 2.98]; p = 0.019). The frequencies of the GSTT1 null genotype in the total group of bladder cancer cases versus controls did not differ statistically. However, a significantly higher relative risk of bladder cancer for the GSTT1 null genotype was detected in the cases-subgroup of non-smokers (OR = 3.84; 95% CI [1.21, 12.23]; p = 0.023). Thus, the GSTT1 null genotype might represent a minor risk factor for human bladder cancer which should be further investigated. Received: 2 May 1996 / Accepted: 16 July 1996     

Growth retardation of fetal rats exposed to nicotine in utero: possible involvement of CYP1A1, CYP2E1, and P-glycoprotein

To elucidate the possible metabolic mechanism of intrauterine growth retardation induced by nicotine, this study determines the effects of prenatal nicotine exposure on fetal development and cytochrome P4501A1 (CYP1A1), CYP2E1, and P-glycoprotein (Pgp) expression in maternal liver and placenta. Pregnant rats were given 1.0 mg/kg nicotine subcutaneously twice a day from gestational day (GD) 8 to GD 15, 18, or 21. In nicotine-treated groups, fetal developmental parameters including body weight were significantly lower. The activities of CYP1A1 and CYP2E1 in maternal liver microsomes in nicotine-treated groups increased significantly with progressing gestation when compared with the corresponding control, but returned to the level similar to the control in late pregnancy. Nicotine-treated groups induced pathological changes and increased malondialdehyde (MDA) content in the placenta when compared with the control. The gene expressions of CYP1A1 and CYP2E1 in the placenta increased significantly in nicotine-treated groups on GD 15 and GD 18, but returned to the level similar to the corresponding control on GD 21. In nicotine group, there was a decrease of mdr1a expression on GD 15, GD 18, and GD 21, with the most significant decrease on GD 15. In contrast, no significant difference was found in mdr1b mRNA expression between the nicotine-treated animals and the corresponding control. In comparison with the corresponding control, the placental Pgp protein significantly decreased on GD 15 and GD 18. Our results showed that prenatal nicotine exposure resulted in inhibition of fetal growth significantly. The induction of CYP2E1 and CYP1A1 gene expression by nicotine in the maternal liver and placenta may be involved with the observed increase in oxidative stress and lipid peroxidation. The inhibition of the placental Pgp expression by nicotine may also contribute to an increased susceptibility of the fetus to environmental toxins.     

Propoxur-induced oxidative DNA damage in human peripheral blood mononuclear cells: protective effects of curcumin and α-tocopherol

The present study enumerates the attenuating effects of curcumin and α-tocopherol against propoxur induced oxidative DNA damage in human peripheral blood mononuclear cells (PBMC). Cultured cells were isolated from peripheral blood of healthy volunteers, and were exposed to varying concentrations of propoxur (0–21?μg/ml) for 6, 12, and 24?h, and in combination with curcumin (9.2?μg/ml) or α-tocopherol (4.3?μg/ml) or both. Cytotoxic effect of propoxur was examined by MTT assay. The role of oxidative stress beneath the cytotoxicity of propoxur was evaluated by the measurement of reduced glutathione (GSH), malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OH-dG) levels in cell lysate. A concentration-dependent cell death, depletion of GSH, an increase in the level of both MDA and 8-OH-dG were observed. Co-treatment with curcumin or α-tocopherol significantly attenuates depleted GSH, decrease in MDA and 8-OH-dG levels in propoxur exposed cells (p?相似文献   

Influence of polymorphisms of GSTM1 and GSTT1 for risk of renal cell cancer in workers with long-term high occupational exposure to trichloroethene

Suspected nephrocarcinogenic effects of trichloroethene (TRI) in humans are attributed to metabolites derived from the glutathione transferase (GST) pathway. The influence of polymorphisms of GSTM1 and GSTT1 isoenzymes on the risk of renal cell cancer in subjects having been exposed to high levels of TRI over many years was investigated. GSTM1 and GSTT1 genotypes were determined by internal standard controlled polymerase chain reaction. Fourty-five cases with histologically verified renal cell cancer and a history of long-term occupational exposure to high concentrations of TRI were studied. A reference group consisted of 48 workers from the same geographical region with similar histories of occupational exposures to TRI but not suffering from any cancer. Among the 45 renal cell cancer patients, 27 carried at least one functional GSTM1 gene (GSTM1+) and 18 at least one functional GSTT1 gene (GSTT1+). Among the 48 reference workers, 17 were GSTM1+ and 31 were GSTT1+. Odds ratios for renal cell cancer were 2.7 for GSTM1+ individuals (95% CI, 1.18–6.33; P < 0.02) and 4.2 for GSTT1+ individuals (95% CI, 1.16–14.91; P < 0.05), respectively. The data support the present concept of the nephrocarcinogenicity of TRI. Received: 20 March 1997 / Accepted: 28 April 1997     

Measuring problems in estimating the exposure to passive smoking using the excretion of cotinine

Quality control studies on cotinine measurements following low level environmental tobacco smoke (ETS) exposure are rare. The exposure to ETS was controlled and systematically changed in a series of experiments in a climatic chamber. Healthy nonsmoking volunteers were exposed to ETS simultaneously. The duration and level of exposure varied using high (8, 17 and 25 ppm CO), and low (2 and 5 ppm CO) exposure levels. The variation between radioimmunoassay (RIA) and gas chromatography (GC) was high as was the variation between the results of RIA laboratories. There was also a high within-laboratory-variation. A 1:10 dilution seems to be preferable over a 1:3 dilution. Freezing the urine samples immediately after collection led to the detection of higher cotinine values than freezing the samples 24 h after collection. Highly reliable data for cotinine were obtained when the urine samples were kept frozen immediately after collection and fractionated sampling over 48-72 h was used. Our data show that estimating low-level ETS exposure by measuring urinary cotinine is highly susceptible to uncontrolled variation and errors. Sufficiently reliable estimates of low-level ETS exposure can be made only when fractionated sampling over 48-72 h is used and when the urine samples are kept frozen just after collection.     

Assessment of prenatal tobacco smoke exposure by determining nicotine and its metabolites in meconium

Meconium samples collected from 115 neonates were analysed for nicotine, cotinine and trans -3-hydroxycotinine (OH-cotinine) by means of high-performance liquid chromatography (HPLC) to identify prenatal smoke exposure. The self-reported maternal smoking status during pregnancy was determined by means of a questionnaire and verified by measurements in urine prior to childbirth. The total sum of nicotine and its metabolites (Sum(tot)) of the first passed meconium samples was 1560 +/- 1024 pmol/g in newborns of smoking mothers. Smoking of less than five cigarettes was clearly detected. Sum(tot) remained constant in all meconium samples passed by a neonate in succession. However, the proportion of nicotine decreased with the time of passage after birth and the OH-cotinine proportion increased, whereas cotinine hardly changed. Nicotine or its metabolites were not detectable in meconium (detection limit < 20 pmol/g), when the mothers were only exposed to environmental tobacco smoke (ETS) using the HPLC method. The hypothesis that the content of nicotine metabolites in meconium reflects long-term smoke exposure could not be confirmed in newborns whose mothers had quit smoking during the latter half of pregnancy. Determining Sum(tot) enables the intensity of continuous smoking during pregnancy to be estimated in all meconium samples passed by a newborn.     

Glutathione S-transferase M1 and T1 null allele frequencies among Indonesian ethnics toward improved disease risk assessment

Genetic variations in the glutathione S-transferase genes GSTT1 and GSTM1 have been widely studied, and homozygous deletions or null genotypes have been reported in different populations. Previous studies suggest that individuals who are homozygous-null at the GSTM1 or GSTT1 locus may have an increased risk of environmentally related cancers and drug-induced hepatotoxicity. The aim of the present study was to determine the GSTM1 and GSTT1 polymorphisms in 154 healthy, unrelated individuals from the Javanese-Sundanese and Malay ethnic populations of Indonesia to provide a resource for improving the prognosis of possible susceptibilities in specific populations. The subjects were genotyped for the presence of GSTM1 and GSTT1 using the multiplex polymerase chain reaction technique. The GSTM1-null genotype was more frequent among Javanese-Sundanese ethnics (99%) than among the Indonesian Malay (67.2%). Similarly, Javanese-Sundanese ethnics showed a higher frequency of the GSTT1-null genotype (66.7%) than the Indonesian Malay (36.2%). Analysis of the combined distribution of the GSTM1 and GSTT1 genes revealed that 66.7% of the individuals from the Javanese-Sundanese population lack both the genes, whereas only 21.1% of the Indonesian Malay is GSTM1-null and GSTT1-null. This study contributes significant information on the variability of GSTT1 and GSTM1 gene polymorphisms worldwide, which can provide new knowledge about the relationship between ethnicity and the prevalence of certain diseases.     

Role of polymorphic GSTM1 and GSTT1 genotypes on NNK-induced genotoxicity

Polymorphisms in chemical metabolizing genes are known to influence individual susceptibility to environmental cancer. We investigated the role of GSTM1 and GSTT1 polymorphisms in modifying the genotoxicity of a tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) using the sister chromatid exchange (SCE), and the tandem-probe fluorescence in situ hybridization chromosome aberration (CA) assays. NNK (0.24, 0.72 or 1.44 mM) induced a significant concentration-dependent increase in the mean number of SCE regardless of genotypes. In comparing the effects between genotypes, significant increase was observed in GSTM1 null cells compared with GSTM1 positive cells only at the low concentration of NNK (0.24 mM). No significant difference was observed between cells with the null and positive GSTT1 genotypes. Using the CA assay, treatment with NNK (0.12, 0.24 or 0.72 mM) induced a significant concentration-dependent increase in the frequency of CA. In addition, cells with the null GSTM1 genotype had significantly increased CA compared with cells with GSTM1 positive genotype at the three concentrations of NNK. Regarding GSTT1 polymorphism, no significant effect was observed between the null and the positive genotypes. Treatment of the cells with 1 mM glutathione monoethyl ester (GSHME) significantly reduced NNK-induced CA in all cells regardless of their genotypes. The effect was clearly more evident in cells with the GSTM1 positive genotype. Therefore, GSHME is protective against NNK-induced CA with more dominant effect in cells with the GSTM1 positive genotype. Our study indicates that GSTM1 may influence NNK-induced genotoxicity and subsequent tobacco-related health effects.     

Assessment of the exposure of children to environmental tobacco smoke (ETS) by different methods.

1. In order to elucidate the role of exposure to environmental tobacco smoke (ETS) in various acute and chronic illnesses in children, it is important to assess the degree of exposure by suitable methods. For this purpose, we determined the exposure to ETS in 39 children (4-15 years) and 43 adults (16+ years) by questionnaires, personal diffusion samplers for nicotine, and cotinine measurements in saliva and urine. In addition, the influence of the smoking status and the location of the home (urban or suburban) on the benzene exposure of the children was investigated. 2. On average, the 24 children living in homes with at least one smoker were exposed to ETS for 3.1 h/d. This is significantly longer (P<0.001) than the daily exposure time of the 15 children from nonsmoking homes (0.3 h/d). The nicotine concentrations on the personal samplers worn over 7 days were 0.615 and 0.046 microg/m3 for children from smoking and nonsmoking homes, respectively (P<0.001). Average salivary cotinine levels were 1.95 ng/ml in children from smoking homes and 0.11 ng/ml in children from nonsmoking homes (P< 0.01). The corresponding urinary cotinine levels were 29.4 and 4.5 ng/mg creatinine (P< 0.001). There was no difference in the extent of ETS exposure between children and adults from smoking households. Adults from nonsmoking homes tended to have higher ETS exposure than children from nonsmoking homes. 3. Exposure to benzene, which was determined by means of personal samplers, measurements of benzene in exhaled air and of the urinary benzene metabolite trans, trans-muconic acid, was not significantly related to the smoking status of the home but primarily dependent on the location of the home.