Aromatic DNA adducts in lymphocytes of humans working at high and low traffic density areas

doi:10.1016/0009-2797(96)03720-9

Chemico-Biological Interactions

Volume 101, Issue 2, 14 August 1996, Pages 127-136

https://doi.org/10.1016/0009-2797(96)03720-9 Get rights and content

Abstract

Aromatic DNA adduct levels were determined by the ³²P-postlabelling assay in lymphocytes isolated from newspaper vendors working at urban high traffic areas (n = 31) and suburban low traffic areas (n = 22) in Milan, Italy. The DNA adduct levels ranged from 0.7 to $6.7 10^{8}$ nucleotides, while most of them were between 1.0 and $3.0 10^{8}$ nucleotides. No difference was found between the DNA adduct levels of the high-exposed group ( $2.2 10^{8}$ ) and the low-exposed group ( $2.2 10^{8}$ ). The heavy smokers (n = 8) had 23% higher DNA adduct level ( $2.7 10^{8}$ ) than the non-smokers (n = 37, $2.2 10^{8}$ ) (P = 0.27), but no correlation was found between the adduct level and the number of cigarettes/day. Analysis of variance of the DNA adduct levels among the 14 pairs of individuals working at the same news-stands revealed little effect of the environmental air exposure on the DNA adduct level.

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Exposure to ambient air pollution has been associated with cancer. Ambient air contains a complex mixture of toxics, including particulate matter (PM) and benzene. Carcinogenic effects of PM may relate both to the content of PAH and to oxidative DNA damage generated by transition metals, benzene, metabolism and inflammation.
By means of personal monitoring and biomarkers of internal dose, biologically effective dose and susceptibility, it should be possible to characterize individual exposure and identify air pollution sources with relevant biological effects. In a series of studies, individual exposure to PM_2.5, nitrogen dioxide (NO₂) and benzene has been measured in groups of 40–50 subjects. Measured biomarkers included 1-hydroxypyrene, benzene metabolites (phenylmercapturic acid (PMA) and trans-trans-muconic acid (ttMA)), 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) in urine, DNA strand breaks, base oxidation, 8-oxodG and PAH bulky adducts in lymphocytes, markers of oxidative stress in plasma and genotypes of glutathione transferases (GSTs) and NADPH:quinone reductase (NQO1).
With respect to benzene, the main result indicates that DNA base oxidation is correlated with PMA excretion. With respect to exposure to PM, biomarkers of oxidative damage showed significant positive association with the individual exposure. Thus, 8-oxodG in lymphocyte DNA and markers of oxidative damage to lipids and protein in plasma associated with PM_2.5 exposure. Several types of DNA damage showed seasonal variation. PAH adduct levels, DNA strand breaks and 8-oxodG in lymphocytes increased significantly in the summer period, requiring control of confounders. Similar seasonal effects on strand breaks and expression of the relevant DNA repair genes ERCC1 and OGG1 have been reported.
In the present setting, biological effects of air pollutants appear mainly related to oxidative stress via personal exposure and not to urban background levels. Future developments include personal time-resolved monitors for exposure to ultrafine PM and PM_2.5, use of GPS, as well as genomics and proteomics based biomarkers.
Newsagents' daily personal exposures to benzo(a)pyrene in Genoa, Italy
2003, Atmospheric Environment
Daily personal exposures to benzo(a)pyrene (BaP) of 31 newsagents working in Genoa, Italy, were evaluated throughout 1998 during two different seasonal periods (February–April and May–June). Exposures of smoker and non-smoker subjects were compared.
The highest BaP exposures were those of smokers during the cold period (2.20±0.84 ng/m³). During this same period, the BaP exposure for non-smoker subjects was 1.00±0.32 ng/m³. Both smoker and non-smoker exposures showed a seasonal dependence, with the lowest values occurring in the warm period (smokers: 1.46±0.72 ng/m³, non-smokers: 0.65±0.25 ng/m³). Compared to the cold period, the warm period produced a nearly 35% reduction in BaP exposures in both smoker and non-smoker subjects.
A linear correlation was observed between personal exposures and number of cigarettes smoked daily. An increase in average daily BaP exposure of 0.071±0.009 ng/m³ for every cigarette, due to passive smoke, was calculated.
Mean BaP concentrations calculated from fixed monitoring stations were nearly 40% higher than mean personal exposures of non-smoker newsagents.
Effect of genotype on steady-state CYP1A1 gene expression in human peripheral lymphocytes
2003, Biochemical Pharmacology
Citation Excerpt :
Similar negative results for the effects of smoking were reported for CYP1A1 gene expression [15], and for expression of other genes [16,17] in Caucasians. Other biomarker endpoints such as DNA adducts and chromosomal or cytogenetic markers are often associated with smoking to a lesser extent in PBL than in other tissues, and/or to an extent less than would be expected if PBL were a truly useful surrogate tissue for the effects of smoking [18–23]. We observed that the steady-state level of CYP1A1 mRNA in PBL of women was almost twice that of men, confirming an earlier report by Mollerup et al. [24] that used a different quantitative PCR methodology.
We have analyzed the steady-state levels of cytochrome P-450 1A1 (CYP1A1) mRNA in peripheral blood lymphocytes of 177 individuals with various CYP1A1 genotypes using a quantitative reverse transcriptase–polymerase chain reaction technique that makes use of a homologous internal standard for accurate quantitation. We found no effects of ethnicity, age, or smoking status on CYP1A1 gene expression in this population. We did see a significant 2-fold increase in the mean level of CYP1A1 mRNA in women compared with men for both Caucasians and African Americans. We observed no effect of the African American-specific polymorphism (CYP1A1^∗3) on expression of the gene. However, we found a significant 3-fold decrease in expression associated with the homozygous MspI restriction fragment length polymorphism (CYP1A1^∗2A/^∗2A).
Aromatic DNA adduct levels in coke oven workers: Correlation with polymorphisms in genes GSTP1, GSTM1, GSTT1 and CYP1A1
2002, Mutation Research - Genetic Toxicology and Environmental Mutagenesis
The aim of this study was to use DNA adducts levels, detected by $^{32} P$ -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 10⁸ 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 10⁸ 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 10⁸ nucleotides, P<0.05), but no effect was observed for the GST genotypes studied.
Biomarkers of genotoxicity of urban air pollution: Overview and descriptive data from a molecular epidemiology study on populations exposed to moderate-to-low levels of polycyclic aromatic hydrocarbons: The AULIS project
2001, Mutation Research - Genetic Toxicology and Environmental Mutagenesis
Epidemiologic studies indicate that prolonged exposure to high pollution levels is associated with increased risk of cancer, especially lung cancer. However, under conditions of moderate or low air pollution, epidemiologic evidence does not permit reliable conclusions. Biomarker-based population studies may serve as complementary tools providing a better understanding of the relative contribution of ambient atmospheric pollution to the overall genotoxic burden suffered by city dwellers. However, past efforts to apply biomarkers to studies of low levels exposure to urban air pollution have given inconclusive results, partly because of the absence of adequate data on personal exposure, covering a time-window which is appropriate for the biomarkers being examined, as well as a battery of biomarkers reflecting different stages of the carcinogenic process.
In the present paper, the potential of biomarker-based population studies to aid the assessment of the genotoxic and carcinogenic effects of urban air pollution is reviewed by reference to the achievements and limitations of earlier reported studies. The design and methodology adopted in a recently completed large-scale population study, carried out in the context of the European Union Environment and Climate Programme, known by the short name of AULIS project,¹ is discussed and descriptive statistics of the main findings of the project are presented. These findings indicate that for cohorts suffering moderate-to-low exposures to airborne particulate-bound polycyclic aromatic hydrocarbons (PAHs), no simple correlation with biomarkers of genotoxicity existed and suggest that additional factors made a significant contribution to the overall genotoxic burden.
The effect of the genetic polymorphisms of CYP1A1,CYP2D6, GSTM1 and GSTP1 on aromatic DNA adduct levels in the population of healthy women
2000, Mutation Research - Genetic Toxicology and Environmental Mutagenesis
Aromatic DNA adduct levels and polymorphisms of two phase I enzymes — CYP1A1 and CYP2D6 and two phase II enzymes — GSTM1 and GSTP1 were analyzed in a group of 133 nonsmoking healthy women 35–45 years old and holding jobs not connected with the exposure to the combustion products of organic matter. They were office workers from the south and north-eastern parts of Poland. Blood samples were collected in winter and in summer. Aromatic DNA adduct levels were measured in all winter and summer samples. The frequencies of CYP1A1, CYP2D6, GSTM1 and GSTP1 polymorphisms in samples from the studied women did not show any differences when compared with other Caucasian populations and the Polish male population studied previously. The differences in the levels of DNA adducts among the carriers of different genotypes were statistically non-significant. Analysis of combined genotypes selected the groups of volunteers with the highest and the lowest DNA adduct levels. The highest levels of DNA adducts were observed in the carriers of GSTM1(null)/CYP1A1Ile/Val (8.00±13.00 adducts/10⁸ nucleotides in summer samples) and GSTP1-AA/CYP1A1Ile/Val genotypes (7.00±4.32 in winter and 7.30±7.27/10⁸ nucleotides in summer). The lowest levels of DNA adducts (3.00±2.30 in winter and 2.00±3.16/10⁸ nucleotides in summer) were found in the carriers of the genotype GSTP1-AG+GG/CYP1A1Ile/Val. The levels of DNA adducts in these groups were determined by the polymorphisms of GSTM1 and GSTP1 phase II detoxifying enzymes.

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Aromatic DNA adducts in lymphocytes of humans working at high and low traffic density areas

Abstract

Toxicol. Lett.

Mutat. Res.

Correlation of DNA adduct levels in human lung with cigarette smoking

Nature

DNA adducts, mutations and cancer

Carcinogenesis

Human biomonitoring and the 32P-postlabelling assay

Carcinogenesis

Complex Mixtures and Human Biomonitoring

32P-postlabelling test for DNA damage

Enhanced sensitivity of 32P-postlabelling analysis of aromatic carcinogen:DNA adducts

Cancer Res.

Nuclease P1-mediated enhancement of sensitivity of 32P-postlabelling test for structurally diverse DNA adducts

Carcinogenesis

Tobacco Smoking

Mechanism of chemical Carcinogenesis

Cancer

Polynuclear Aromatic Compounds, Part 3, Industrial Exposures in Aluminium Production, Coal Classification, Coke Production and Iron and Steel Founding

Environ. Health Perspect.

Seasonal variation of aromatic DNA adducts in human lymphocytes and granulocytes

Carcinogenesis

Cancer risk of air pollution: epidemiological evidences

Environ. Health Perspect.

Aromatic DNA adducts in human bone marrow and peripheral blood leukocytes

Carcinogenesis

Human biomonitoring and the ³²P-postlabelling assay

³²P-postlabelling test for DNA damage

Enhanced sensitivity of ³²P-postlabelling analysis of aromatic carcinogen:DNA adducts

Nuclease P1-mediated enhancement of sensitivity of ³²P-postlabelling test for structurally diverse DNA adducts