Biomarkers of genetic damage and inflammation in blood and bronchoalveolar lavage fluid among former German uranium miners: a pilot study

Abstract

Former East German uranium miners who are known to have been exposed to radon are estimated to be at high risk for lung carcinogenesis. Among these miners over 200 occupationally caused lung cancer cases are expected to occur each year, resulting in a total of 7,000-24,000 excess lung cancer cases in the coming years. It is still unknown whether there is a correlation between biomarkers and the exposure of the uranium miners to ionizing radiation that might enable us to trace those miners with high lung cancer risk. The primary aim of this pilot study was to test the possibility of performing a biomarker study in this unique cohort of former uranium miners in spite of several limitations that had to be taken into consideration when comparing them with healthy controls, such as old age, age-dependent diseases and potential confounding artefacts from dissimilar smoking patterns. The second aim was to test a range of biomarkers for DNA damage and inflammation in leukocytes and bronchoalveolar fluid for their ability to detect biological effects. In this cohort of miners we found an increased frequency of chromosomal aberrations in blood lymphocytes and an increased prevalence of both fibronectin and tumour necrosis factor alpha in the bronchoalveolar fluid.

Micronuclei in lymphocytes of uranium miners of the former Wismut SDAG

“…1) and as published previously (Popp et al, 2000), we did not find statistically significant differences in micronucleus frequencies among the various groups analyzed (controls, uranium miners, lung tumor patients, and patients with lung fibrosis). An interesting question is, of course, whether the amount of radiation exposure is reflected by the number of micronuclei found in the peripheral lymphocytes of the uranium miners.…”

“…Information on the various groups analyzed in the pilot study of the usefulness of biomarkers in uranium miners have also been published (Popp et al, 2000). The Wismut group comprised 106 individuals; for various reasons, only 85 could be included in the analyses presented in this article.…”

“…Some years ago, we, together with a couple of other groups, published results of a biomarker study in former German uranium miners (Popp et al, 2000). Our contribution to this study was, among some other endpoints, the evaluation of micronuclei in peripheral lymphocytes.…”

“…The publication mentioned above (Popp et al, 2000) was intended as a pilot study comparing various biomarkers and, thus, did not give very detailed information on the micronucleus results. This will be done in the article presented here.…”

Measures of genotoxicity in Gulf war I veterans exposed to depleted uranium

“…Challenge assay suggests a decrease in DNA repair. Zaire et al, 1997 CAs in whole blood cells using FISH in Namibia uranium miners 3-fold increase in CAs in nonsmoking, HIV-negative miners, including cells with multiple aberrations (''rogue'' cells) Popp et al, 2000 Lung macrophage collected from former German miners The hierarchy of evidence considered in carcinogenicity assessments by the International Agency for Research on Cancer (IARC) and other bodies is established with human epidemiology and whole animal studies taking precedence over in vivo genotoxicity testing and in vitro and cell culture/system testing [Montesano, 1986;Vainio et al, 1992; International Agency for Research on Cancer (IARC), 2006] and must be drawn upon to understand the meaning of the available data. Thus, the battery of generally negative in vivo genotoxicity measures we have collected in this DU-exposed cohort, in the context of negative epidemiological evidence for human cancer excesses, suggests there is little evidence for the potential of carcinogenicity in DU-exposed veterans.…”