Biomarkers for exposure to ambient air pollution--comparison of carcinogen-DNA adduct levels with other exposure markers and markers for oxidative stress.

Human exposure to genotoxic compounds present in ambient air has been studied using selected biomarkers in nonsmoking Danish bus drivers and postal workers. A large interindividual variation in biomarker levels was observed. Significantly higher levels of bulky carcinogen-DNA adducts (75.42 adducts/10(8) nucleotides) and of 2-amino-apidic semialdehyde (AAS) in plasma proteins (56.7 pmol/mg protein) were observed in bus drivers working in the central part of Copenhagen, Denmark. In contrast, significantly higher levels of AAS in hemoglobin (55.8 pmol/mg protein), malondialdehyde in plasma (0. 96 nmol/ml plasma), and polycyclic aromatic hydrocarbon (PAH)-albumin adduct (3.38 fmol/ microg albumin) were observed in the suburban group. The biomarker levels in postal workers were similar to the levels in suburban bus drivers. In the combined group of bus drivers and postal workers, negative correlations were observed between bulky carcinogen-DNA adduct and PAH-albumin levels (p = 0.005), and between DNA adduct and [gamma]-glutamyl semialdehyde (GGS) in hemoglobin (p = 0.11). Highly significant correlations were found between PAH-albumin adducts and AAS in plasma (p = 0.001) and GGS in hemoglobin (p = 0.001). Significant correlations were also observed between urinary 8-oxo-7, 8-dihydro-2'-deoxyguanosine and AAS in plasma (p = 0.001) and PAH-albumin adducts (p = 0.002). The influence of the glutatione S-transferase (GST) M1 deletion on the correlation between the biomarkers was studied in the combined group. A significant negative correlation was only observed between bulky carcinogen-DNA adducts and PAH-albumin adducts (p = 0.02) and between DNA adduct and urinary mutagenic activity (p = 0.02) in the GSTM1 null group, but not in the workers who were homozygotes or heterozygotes for GSTM1. Our results indicate that some of the selected biomarkers can be used to distinguish between high and low exposure to environmental genotoxins

Stomach cancer and occupational exposure to asbestos: a meta-analysis of occupational cohort studies

BACKGROUND: A recent Monographs Working Group of the International Agency for Research on Cancer concluded that there is limited evidence for a causal association between exposure to asbestos and stomach cancer. METHODS: We performed a meta-analysis to quantitatively evaluate this association. Random effects models were used to summarise the relative risks across studies. Sources of heterogeneity were explored through subgroup analyses and meta-regression. RESULTS: We identified 40 mortality cohort studies from 37 separate papers, and cancer incidence data were extracted for 15 separate cohorts from 14 papers. The overall meta-SMR for stomach cancer for total cohort was 1.15 (95% confidence interval 1.03–1.27), with heterogeneous results across studies. Statistically significant excesses were observed in North America and Australia but not in Europe, and for generic asbestos workers and insulators. Meta-SMRs were larger for cohorts reporting a SMR for lung cancer above 2 and cohort sizes below 1000. CONCLUSIONS: Our results support the conclusion by IARC that exposure to asbestos is associated with a moderate increased risk of stomach cancer

Nonpulmonary Outcomes of Asbestos Exposure

The adverse pulmonary effects of asbestos are well accepted in scientific circles. However, the extrapulmonary consequences of asbestos exposure are not as clearly defined. In this review the potential for asbestos to produce diseases of the peritoneum, immune, gastrointestinal (GIT), and reproductive systems are explored as evidenced in published, peer-reviewed literature. Several hundred epidemiological, in vivo, and in vitro publications analyzing the extrapulmonary effects of asbestos were used as sources to arrive at the conclusions and to establish areas needing further study. In order to be considered, each study had to monitor extrapulmonary outcomes following exposure to asbestos. The literature supports a strong association between asbestos exposure and peritoneal neoplasms. Correlations between asbestos exposure and immune-related disease are less conclusive; nevertheless, it was concluded from the combined autoimmune studies that there is a possibility for a higher-than-expected risk of systemic autoimmune disease among asbestos-exposed populations. In general, the GIT effects of asbestos exposure appear to be minimal, with the most likely outcome being development of stomach cancer. However, IARC recently concluded the evidence to support asbestos-induced stomach cancer to be “limited.” The strongest evidence for reproductive disease due to asbestos is in regard to ovarian cancer. Unfortunately, effects on fertility and the developing fetus are under-studied. The possibility of other asbestos-induced health effects does exist. These include brain-related tumors, blood disorders due to the mutagenic and hemolytic properties of asbestos, and peritoneal fibrosis. It is clear from the literature that the adverse properties of asbestos are not confined to the pulmonary system

Incidence of cancer and mortality among employees in the asbestos cement industry in Denmark.

In a cohort study of the incidence of cancer and mortality among 7996 men and 584 women employed in the Danish asbestos cement industry between 1928 and 1984 over 99% were traced. Chrysotile asbestos was the only fibre type used until 1946, when amosite and (in 1952) crocidolite were also introduced. Chrysotile constituted 89%, amosite 10%, and crocidolite 1% of the asbestos used. During the first 25 years of manufacture the exposure levels were high, especially in areas where the asbestos was handled dry. Measurements from 1948 indicate that the fibre levels may have ranged from 100 to 1600 times over the present Danish threshold limit value of 0.5 fibre/ml. In 1973 more than 41% of personal samples were higher than 2 f/ml. About 76% of the workforce left the factory within five years of starting employment. A total of 1346 deaths and 612 cases of cancer were observed in the cohort between 1943 and 1984. Among employed men the overall mortality (O/E 1.18; 95% CI 1.12-1.25), cancer mortality (O/E 1.32; 95% CI 1.19-1.46), and overall incidence of cancer (O/E 1.22; 95% CI 1.12-1.32) were significantly increased compared with all Danish men. This was not so among employed women. For men, significant excess risks were found for cancer of the lung (O/E 1.80; 95% CI 1.54-2.10), pleura (O/E 5.46; 95% CI 2.62-10.05), mediastinum (O/E 5.00; 95% CI 1.01-14.61), stomach (O/E 1.43; 95% CI 1.03-1.93), and other male genital organs (O/E 3.03; 95% CI 1.11-6.60). The mortality was significantly increased for men for non-malignant pulmonary diseases (O/E 1.63; 95% CI 1.33-1.98). Among the group of asbestos cement workers with first employment 1928-40 an excess risk of laryngeal cancer was found (O/E 5.50;95% CI 1.77-12.82). A total of 12 cases of pleural and one of peritoneal mesotheliomas was observed when the original notification forms were reviewed for all patients with cancer in the cohort

Exposure to cement dust at a Portland cement factory and the risk of cancer.

The relation between exposure to cement dust and cancer was examined in a population of 546 cement workers and a reference population of 858 randomly sampled men of similar age and area of residence. In 1974 all men gave lifelong occupational and smoking histories; information on incidence of cancer in the period 1974-85 was obtained from the Danish Cancer Registry. No increased risk of overall cancer was found among cement workers. Among men with more than 20 years exposure to cement dust, 14 cases of respiratory cancer were observed (observed/expected (O/E) 1.52, 95% confidence interval (95% CI) 0.90-2.57) when compared with all Danish men. Men with 1-20 years exposure had O/E 1.14 (95% CI 0.59-2.19) based on nine cases of cancer. After excluding all men with documented exposure to asbestos during employment in an asbestos cement factory no increased risk of overall cancer or respiratory cancer was found among cement workers compared with white collar workers from the local reference population, using a Cox regression model controlling for age and smoking habits. Relative risks were 0.5 (95% CI 0.1-1.5) and 1.0 (95% CI 0.4-2.6) for men with 1-20 and more than 20 years of exposure to cement dust respectively compared with white collar workers