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ABSTRACT: Formaldehyde (FA) is a widely used industrial chemical for which exposure is associated with nasopharyngeal and sinonasal cancer. Based on sufficient evidence of carcinogenicity from human investigations, supporting studies on mechanisms underlying carcinogenesis, and experimental evidence in animals, FA status was recently revised and reclassified as a human carcinogen. The highest level of exposure to FA occurs in occupational settings. Although several studies reported FA ability to induce genotoxic responses in exposed workers, not all findings were conclusive. In addition, published studies on the immunological effects of FA indicate that this compound may be able to modulate immune responses, although data in exposed subjects are still preliminary. In this study a group of pathology anatomy workers exposed to FA was evaluated for cytogenetic and immunological parameters. A control group with similar sociodemographic characteristics and without known occupational exposure to FA was also included. Genotoxicity was evaluated by means of micronucleus (MN) test, sister chromatid exchanges (SCE), and T-cell receptor (TCR) mutation assay. Percentages of different lymphocyte subpopulations were selected as immunotoxic biomarkers. The mean level of FA environmental exposure was 0.36 ± 0.03 ppm. MN and SCE frequencies were significantly increased in the exposed group. A significant decrease of the percentage of B cells in the exposed group was also found. Data obtained in this study indicate that genotoxic and immunotoxic increased risk due to FA occupational exposure cannot be excluded. Implementation of effective control measures along with hazard prevention campaigns may be crucial to decrease the risk.
Journal of Toxicology and Environmental Health Part A 01/2013; 76(4-5):217-29. · 1.83 Impact Factor
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ABSTRACT: The age of the European population is rising and percentage of adults aged 65 years and older is projected to increase from 16% in 2000 to 20% in 2020. It has been estimated that older subjects spend approximately 19 to 20 h/d indoors. Older individuals may be particularly at risk for detrimental effects from pollutants, even at low concentrations, due to reduced immunological defenses and multiple underlying chronic diseases. Six Porto, Portugal, urban area elderly care centers (ECC), housing a total of 425 older persons, were studied to assess indoor air quality (IAQ) and thermal comfort (TC) in two seasons. This study presents the IAQ and TC results in 36 rooms and constitutes part of a wider and ongoing study. The study areas were all naturally ventilated, and indoor concentrations in winter were within Portuguese reference values. However, 42% of the participants were dissatisfied with indoor thermal conditions, rating it "slightly cool." In summer, the index rate of dissatisfied individuals was lower (8%). Significant differences were found between seasons in predicted percent of dissatisfied people (PPD) and predicted mean vote (PMV) indices. Fungal concentrations frequently exceeded reference levels (>500 colony-forming units [CFU]/m(3)). In addition, other pollutants occasionally exceeded reference levels. To our knowledge, this is the first study in Portugal to assess effects of indoor air contaminants on the health status and quality of life in older subjects living in ECC. Although IAQ and TC parameters were mostly within reference values, the results suggest a need to improve the balance between IAQ and TC in ECC, a critical environment housing a susceptible population.
Journal of Toxicology and Environmental Health Part A 01/2013; 76(4-5):333-44. · 1.83 Impact Factor
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Patrícia Coelho,
Solange Costa, Susana Silva,
Alan Walter,
James Ranville,
Ana C A Sousa,
Carla Costa,
Marta Coelho,
Julia García-Lestón,
M Ramiro Pastorinho,
Blanca Laffon,
Eduardo Pásaro,
Chris Harrington,
Andrew Taylor,
João Paulo Teixeira
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ABSTRACT: Mining activities may affect the health of miners and communities living near mining sites, and these health effects may persist even when the mine is abandoned. During mining processes various toxic wastes are produced and released into the surrounding environment, resulting in contamination of air, drinking water, rivers, plants, and soils. In a geochemical sampling campaign undertaken in the Panasqueira Mine area of central Portugal, an anomalous distribution of several metals and arsenic (As) was identified in various environmental media. Several potentially harmful elements, including As, cadmium (Cd), chromium (Cr), manganese (Mn), nickel (Ni), lead (Pb), and selenium (Se), were quantified in blood, urine, hair, and nails (toe and finger) from a group of individuals living near the Panasqueira Mine who were environmentally and occupationally exposed. A group with similar demographic characteristics without known exposure to mining activities was also compared. Genotoxicity was evaluated by means of T-cell receptor (TCR) mutation assay, and percentages of different lymphocyte subsets were selected as immunotoxicity biomarkers. Inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma-atomic emission spectrometry (ICP-AES) analysis showed elevated levels of As, Cd, Cr, Mn, and Pb in all biological samples taken from populations living close to the mine compared to controls. Genotoxic and immunotoxic differences were also observed. The results provide evidence of an elevated potential risk to the health of populations, with environmental and occupational exposures resulting from mining activities. Further, the results emphasize the need to implement preventive measures, remediation, and rehabilitation plans for the region.
Journal of Toxicology and Environmental Health Part A 07/2012; 75(13-15):893-908. · 1.83 Impact Factor
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ABSTRACT: Styrene is a widely used chemical in the manufacture of synthetic rubber, resins, polyesters, and plastics. The highest levels of human exposure to styrene occur during the production of reinforced plastic products. The objective of this study was to examine occupational exposure to styrene in a multistage approach, in order to integrate the following endpoints: styrene in workplace air, mandelic and phenylglyoxylic acids (MA + PGA) in urine, sister chromatid exchanges (SCE), micronuclei (MN), DNA damage (comet assay), and genetic polymorphisms of metabolizing enzymes (CYP2E1, EPHX1, GSTM1, GSTT1, and GSTP1). Seventy-five workers from a fiberglass-reinforced plastics factory and 77 unexposed controls took part in the study. The mean air concentration of styrene in the breathing zone of workers (30.4 ppm) and the mean concentration of urinary metabolites (MA + PGA = 443 ± 44 mg/g creatinine) exceeded the threshold limit value (TLV) and the biological exposure index (BEI). Significantly higher SCE frequency rate and DNA damage were observed in exposed workers, but MN frequency was not markedly modified by exposure. With respect to the effect of genetic polymorphisms on different exposure and effect biomarkers studied, an increase in SCE levels with elevated microsomal epoxide hydrolase activity was noted in exposed workers, suggesting a possible exposure-genotype interaction.
Journal of Toxicology and Environmental Health Part A 07/2012; 75(13-15):735-46. · 1.83 Impact Factor
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ABSTRACT: The evaluation of the gender-specific prevalence of cardiovascular risk factors across socioeconomic position (SEP) categories may unravel mechanisms involved in the development of coronary heart disease. Using a sample of 1704 community dwellers of a Portuguese urban center aged 40 years or older, assessed in 1999-2003, we quantified the age-standardized prevalence of nine established cardiovascular risk factors (diabetes mellitus, hypertension, hypercholesterolemia, smoking, sedentariness, abdominal obesity, poor diet, excessive alcohol intake and depression) across SEP and gender categories. Data on individual education and occupation were collected by questionnaire and used to characterize SEP. The prevalence of seven out of nine well-established risk factors was higher in men. Among women, the prevalence of most of the studied risk factors was higher in lower SEP groups. The main exception was smoking, which increased with education and occupation levels. Among men, socioeconomic gradients were less clear, but lower SEP was associated with a higher prevalence of diabetes, excessive alcohol intake and depression in a graded mode. The historical cultural beliefs and practices captured throughout the lifecourse frame the wide socioeconomic gradients discernible in our study conducted in an unequal European developed population. While men were more exposed to most risk factors, the clearer associations between SEP and risk factors among women support that their adoption of particular healthy behaviors is more dependent on material and symbolic conditions. To fully address the issue of health inequalities, interventions within the health systems should be complemented with population-based policies specifically designed to reduce socioeconomic gradients.
PLoS ONE 01/2012; 7(5):e37158. · 4.09 Impact Factor
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ABSTRACT: Formaldehyde (FA) is a world high-production compound with numerous applications ranging from production of resins to medicines. Due to its sensitizing properties, irritating effects and potential cancer hazard FA is of great environmental health concern. Numerous studies in humans and experimental animals demonstrated that inhaled FA produced toxicity, genotoxicity, and cancer at distal sites. IARC, based on sufficient data, reclassified FA as a human carcinogen. The highest level of human exposure to this aldehyde occurs in occupational settings, namely, in pathology and anatomy laboratories, where FA is commonly used as a fixative and tissue preservative. Several studies consistently showed that the levels of airborne FA in anatomy laboratories exceeded recommended exposure criteria. In order to assess the genotoxic effects of chronic occupational exposure to FA, a group of pathology/anatomy workers was assessed using a micronucleus (MN) test and comet assay. The level of exposure to FA was also determined and the time-weighted average (TWA) of exposure was calculated for each subject. The TWA mean value for FA exposed workers was 0.43 ± 0.06 ppm, exceeding national and international recommended limit levels of 0.3 ppm. Both MN frequency and comet assay parameters were significantly higher in exposed subjects. Data obtained confirm a correlation between genetic damage and occupational exposure to FA. These data, along with recent implications of human carcinogenicity, point out the need for close monitoring of occupational exposure to FA. Implementation of security and hygiene measures as well as good practices campaigns may be crucial to decrease risk.
Journal of Toxicology and Environmental Health Part A 08/2011; 74(15-16):1040-51. · 1.83 Impact Factor
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ABSTRACT: A wide range of chemical products known to be acutely toxic is currently used in the agricultural sector, including numerous pesticides with different compositions. Nevertheless, the effects in human health as result of chronic exposure to low levels are not yet completely understood. The methodology for determination of micronuclei (MN) in lymphocytes (CBMN) is well established, and accumulating data demonstrated a correlation to enhanced risk of cancer development. However, analysis of MN in reticulocytes (MN-RET) in humans is a recent tool on human biomonitoring. The aim of this study was to examine the influence of pesticide exposure on MN-RET and CBMN frequencies. In total, 177 individuals were studied (93 controls and 84 exposed). All individuals included in the exposed group were exposed regularly to various chemicals. Both MN-RET and CBMN were significantly higher in the exposed subjects compared to controls. The CBMN frequencies were quantitatively higher in females than males, especially within the exposed group. Smoking habits exerted no marked influence on the frequency of the biomarkers studied. A significant and positive correlation was found between both indicators. Within the exposed group, data showed that there was a significant correlation between MN-RET and recent exposure (exposure in the previous 10 d) that is not found when considering CBMN. It is conceivable that due to the short life span of reticulocytes, MN-RET were found to be more reliable to characterize recent genetic damage as opposed to CBMN.
Journal of Toxicology and Environmental Health Part A 08/2011; 74(15-16):960-70. · 1.83 Impact Factor
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ABSTRACT: MMR is responsible for the repair of base-base mismatches and insertion/deletion loops. Besides this, MMR is also associated with an anti-recombination function, suppressing homologous recombination. Losses of heterozygosity and/or microsatellite instability have been detected in a large number of skin samples from breast cancer patients, suggesting a potential role of MMR in breast cancer susceptibility.
We carried out a hospital-based case-control study in a Caucasian Portuguese population (287 cases and 547 controls) to estimate the susceptibility to non-familial breast cancer associated with some polymorphisms in mismatch repair genes (MSH3, MSH4, MSH6, MLH1, MLH3, PMS1 and MUTYH).
Using unconditional logistic regression we found that MLH3 (L844P, G>A) polymorphism GA (Leu/Pro) and AA (Pro/Pro) genotypes were associated with a decreased risk: OR = 0.65 (0.45-0.95) (p = 0.03) and OR = 0.62 (0.41-0.94) (p = 0.03), respectively.Analysis of two-way SNP interaction effects on breast cancer revealed two potential associations to breast cancer susceptibility: MSH3 Ala1045Thr/MSH6 Gly39Glu - AA/TC [OR = 0.43 (0.21-0.83), p = 0.01] associated with a decreased risk; and MSH4 Ala97Thr/MLH3 Leu844Pro - AG/AA [OR = 2.35 (1.23-4.49), p = 0.01], GG/AA [OR = 2.11 (1.12-3,98), p = 0.02], and GG/AG [adjusted OR = 1.88 (1.12-3.15), p = 0.02] all associated with an increased risk for breast cancer.
It is possible that some of these common variants in MMR genes contribute significantly to breast cancer susceptibility. However, further studies with a large sample size will be needed to support our results.
BMC Cancer 09/2009; 9:344. · 3.01 Impact Factor
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ABSTRACT: Formaldehyde (FA) is a chemical traditionally used in pathology and anatomy laboratories as a tissue preservative. Several epidemiological studies of occupational exposure to FA have indicated an increased risk of nasopharyngeal cancers in industrial workers, embalmers and pathology anatomists. There is also a clear evidence of nasal squamous cell carcinomas from inhalation studies in the rat. The postulated mode of action for nasal tumours in rats was considered biologically plausible and considered likely to be relevant to humans. Based on the available data IARC, the International Agency for Research on Cancer, has recently classified FA as a human carcinogen. Although the in vitro genotoxic as well as the in vivo carcinogenic potentials of FA are well documented in mammalian cells and in rodents, evidence for genotoxic effects and carcinogenic properties in humans is insufficient and conflicting thus remains to be more documented. To evaluate the genetic effects of long-term occupational exposure to FA a group of 30 Pathological Anatomy laboratory workers was tested for a variety of biological endpoints, cytogenetic tests (micronuclei, MN; sister chromatid exchange, SCE) and comet assay. The level of exposure to FA was evaluated near the breathing zone of workers, time weighted average of exposure was calculated for each subject. The association between the biomarkers and polymorphic genes of xenobiotic metabolising and DNA repair enzymes was also assessed. The mean level of exposure was 0.44+/-0.08ppm (0.04-1.58ppm). MN frequency was significantly higher (p=0.003) in the exposed subjects (5.47+/-0.76) when compared with controls (3.27+/-0.69). SCE mean value was significantly higher (p<0.05) among the exposed group (6.13+/-0.29) compared with control group (4.49+/-0.16). Comet assay data showed a significant increase (p<0.05) of TL in FA-exposed workers (60.00+/-2.31) with respect to the control group (41.85+/-1.97). A positive correlation was found between FA exposure levels and MN frequency (r=0.384, p=0.001) and TL (r=0.333, p=0.005). Regarding the genetic polymorphisms studied, no significant effect was found on the genotoxic endpoints. The results of the present biomonitoring study emphasize the need to develop safety programs.
Toxicology 08/2008; 252(1-3):40-8. · 3.68 Impact Factor
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ABSTRACT: The general population is exposed in their everyday life to different chemicals namely to pesticides. Many of these compounds are capable of inducing mutations in DNA and lead to several diseases including cancer. With this study we intended to evaluate DNA damage inflicted by pesticide exposure in a population occupationally exposed to those chemicals by means of the micronucleus (MN) test. The obtained results showed a significant increase in MN frequency in occupationally exposed individuals (p<0.001) compared with the control group. Higher frequencies of MN were associated with a specific workplace (greenhouses) and the lack of protective measures (gloves) during labour activities. These results reinforce that conditions in workplace should be improved to minimize exposure to these chemicals. This study also emphasizes the need to reinforce the good practices campaigns in order to enlighten those who work with pesticides on the potential hazard of occupational exposure and the importance of using protective measures.
International Journal of Hygiene and Environmental Health 05/2007; 210(3-4):415-8. · 3.81 Impact Factor
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ABSTRACT: Campo de Jales is a village surrounding the abandoned Jales mine. The area is heavily contaminated with heavy metals and dusts from large tailings piles as result of centuries of mining operations. The aim of this study is to investigate potential health threats associated with site contamination. The population studied comprised two groups: people living in Campo de Jales (n = 229) and a control group - people living in Vilar de Macada (n = 234). Lead and cadmium exposure and symptoms survey were carried out. The results showed a significant higher levels of blood lead and cadmium between the Campo de Jales residents (lead: 9.5 microgr/dl versus 7.7 microgr/dl; cadmium: 0.84 microgr/dl versus 0,65 microgr/dl) as well as to a higher prevalence of respiratory and irritation symptoms and great concern about his own health. In conclusion: community is the scene of long-term health problems resulting from the site environmental contamination.
Environmental Monitoring and Assessment 01/2007; 123(1-3):31-40. · 1.40 Impact Factor
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ABSTRACT: Widespread use of pesticides in agriculture represents a threat not only to the environment but also to human populations exposed to them. Many of these compounds are capable of inducing mutations in DNA and lead to several diseases including cancer. In the present study, cytogenetic damage in peripheral lymphocytes from 33 farmers of Oporto district (Portugal) exposed to pesticides was evaluated by means of micronuclei (MN), sister chromatid exchange (SCE) and chromosomal aberrations (CA). In addition, effect of polymorphic genes of xenobiotic metabolizing enzymes (GSTM1, GSTT1, GSTP1, CYP2E1 and EPHX1) was also evaluated. A non-exposed group from the same area and with same demographic characteristics without exposure to genotoxic compounds was studied and data obtained from both groups was compared. MN and SCE frequencies were significantly higher in the exposed group (P < 0.005). In what concerns CA results, no significant differences were observed. It was possible to relate a specific working environment (greenhouses) with higher levels of genetic damage. Use of personal protective equipment revealed to be important to prevent exposure and diminish genetic damage inflicted by pesticides. Allele frequencies of studied polymorphic genes obtained in this study are similar to the ones described by other authors for Caucasian populations. Despite the low number of subjects, results suggest that low mEH (microsomal epoxide hydrolase) activity as well as GSTT1 positive genotype are associated with increased cytogenetic damage.
Mutagenesis 10/2006; 21(5):343-50. · 3.18 Impact Factor
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ABSTRACT: A broad spectrum of substances is used in the rubber industry, many of them being genotoxic and/or carcinogenic. Convincing evidence of an excess of certain forms of cancer among rubber workers has been provided. The objective of this study was to determine the genotoxic effects in a group of individuals engaged in the production of rubber tyres from a Portuguese factory. Peripheral blood samples were collected from 32 exposed workers and 32 controls, and micronucleus (MN) test, sister chromatid exchanges (SCE) and comet assay were performed. Urinary thioethers were measured as a general biomarker of exposure to electrophilic compounds, and genetic polymorphisms in metabolizing enzymes (CYP2E1 Dra I, EPHX1 codons 113 and 139, GSTP1 codon 105, and GSTM1 and GSTT1 deletion polymorphisms) were analysed as susceptibility biomarkers. Excretion of thioethers was found significantly higher in rubber workers. Also, a non-significant increase in MN frequency related to time of exposure and no effect in SCE were observed in the exposed. Comet assay data showed decreased TL values in the exposed population with respect to the control group, this might indicate the induction of crosslinks by the substances present in the workplace environment. Significant increase in MN frequency was obtained for GSTT1 null exposed individuals with respect to positive ones, and interaction with GSTP1 polymorphism was found. Higher levels of cytogenetic test frequencies were observed in epoxide hydrolase expected low activity donors with respect to medium and high activity individuals. No effect of CYP2E1 or GSTM1 variants was obtained in the biomarkers analysed.
Annals of Occupational Hygiene 09/2006; 50(6):583-92. · 1.95 Impact Factor
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ABSTRACT: Petroleum refinery workers are potentially exposed to a wide range of petroleum-derived hydrocarbons and chemical substances used in the manufacturing of petroleum derivatives. Benzene, toluene and xylene (BTX) are produced by distillation in the aromatics units and used as raw materials for petrol and petrochemical products. The aim of this study was to evaluate the genotoxic effects of occupational exposure to BTX in a petroleum refinery in the North of Portugal. The exposed group consisted of 48 workers from the aromatics plant and the control group consisted of 30 persons matched for various confounding factors. Chromosome aberrations (CA), micronuclei (MN), and DNA damage (evaluated by means of the comet assay) were measured in peripheral blood leukocytes. t,t-Muconic acid (t,t-MA), hippuric acid (HA) and methylhippuric acid (MHA) concentrations were measured in urine samples collected at the end of the workshift. The results suggest that occupational exposure to toluene and xylene is very low. A statistically significant increase in t,t-MA excretion was found in the exposed group although t,t-MA levels were found to be lower than the biological exposure index (BEI). Significant increases were found for CA, MN and comet tail length (TL) in the exposed group (p<0.05). No association was found between tobacco smoking and the effect biomarkers analysed. A positive association was found between CA and MN with age in the control group (p<0.05).
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 04/2006; 604(1-2):19-27. · 2.85 Impact Factor
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João P Teixeira,
Jorge Gaspar, Susana Silva,
Joana Torres,
Susana N Silva,
M Conceição Azevedo,
Paula Neves,
Blanca Laffon,
Josefina Méndez,
Carla Gonçalves,
Olga Mayan,
Peter B Farmer,
José Rueff
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ABSTRACT: Styrene is widely used in the production of various plastics, synthetic rubber and resins. The aim of this study was to evaluate if individual polymorphisms in xenobiotic metabolizing enzymes, related with the metabolic fate of styrene, could modify individual susceptibility to the possible genotoxic effects of the styrene exposure. Twenty-eight reinforced plastic workers and 28 control subjects were studied. In the selected population the urinary styrene metabolites mandelic (MA) and phenylglyoxylic (PGA) acids were quantified, sister chromatid exchanges (SCE) and micronuclei (MN) were assessed in peripheral lymphocytes and all the subjects were genotyped for GSTM1, GSTT1 (gene deletions), GSTP1 (codon 105 ile==>val), EPHX1 (codons 113 tyr==>his and 139 his==>arg) and CYP2E1 (DraI polymorphism in intron 6). The results obtained showed a significant difference between the levels of SCE, but not in MN levels, in exposed workers as compared with the control group. The GSTP1 and CYP2E1 individual genotypes modulate the baseline levels of SCE that are lower in non-wild type individuals for both polymorphisms. The GSTM1 null individuals with low levels of exposure have significantly higher urinary levels of MA+PGA. The present data seem to suggest that apart from the methodology usually used for monitoring populations occupationally exposed to styrene (urinary metabolites and biomarkers of early biological effects) the analysis of individual genotypes associated with the metabolic fate of styrene should also be carried out in order to evaluate the individual genetic susceptibility of exposed populations.
Toxicology 02/2004; 195(2-3):231-42. · 3.68 Impact Factor
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ABSTRACT: The aim of this study was to use DNA adducts levels, detected by 32P-postlabelling, as a biomarker to assess human exposure to polycyclic aromatic hydrocarbons (PAHs) from a coke oven plant and explore the possible association between CYP1A1 MspI, GSTP1, GSTM1 and GSTT1 genotypes, and smoking status on bulky DNA adduct formation. A large amount of inter-individual variation in adduct level was observed among workers with the same job and the same smoking habits. No significant differences were observed in DNA adduct levels between the coke oven workers and control group. Smokers in the control group had significantly higher DNA adducts than the non-smokers in the same group (35.13+/-21.11 versus 11.18+/-8.00, per 10(8) nucleotides, P=0.003). In this group, the correlation between the level of DNA adducts and the cigarettes smoked was strongly significant (r=0.70, P<0.0005), but no correlation was found among the coke oven workers. Among non-smokers there was a significant difference between the control group and the coke oven workers (11.18+/-8.00 versus 24.62+/-15.20, per 10(8) nucleotides, P=0.03). These results suggests that tobacco smoke could behave as a confounding factor for evaluation of DNA adducts arising from occupational exposure. The levels of DNA adducts in smokers not occupationally exposed to PAHs is dependent on the polymorphisms CYP1A1 MspI in the 3' non-coding region (49.04+/-22.18 versus 25.85+/-15.87, per 10(8) nucleotides, P<0.05), but no effect was observed for the GST genotypes studied.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 06/2002; 517(1-2):147-55. · 2.85 Impact Factor
