Screening for putative radon-specific p53 mutation hotspot in German uranium miners

Biologic damage resulting from exposure to tobacco smoke and from radon: implication for preventive interventions

“…The interaction results in chemical by-products in the cell cytoplasm similar to those produced from exposure to chemical carcinogens such as those contained in tobacco smoke. While the mechanism by which alpha particles cause lung cancer has not been elucidated, a variety of genetic lesions, including chromosomal damage, gene mutations, induction of micronuclei, and sister chromatid exchange (SCE), have been associated with the DNAdamaging effects of alpha particles (Bartsch et al, 1995a;Kennedy et al, 1996;Brooks et al, 1990;Deshpande et al, 1996;Nagasawa and Little, 1992;Wu et al, 1999;Hei et al, 1997Hei et al, , 1998. Emerit et al (1995) found that the classtogenic properties of blood from personnel accidently irradiated at the Chernobyl nuclear power regressed and nearly completed disappeared after treatment with the extract of Ginkgo biloba, which is known for it superoxide scavenging properties.…”

Serum levels of pantropic p53 protein and EGF-receptor, and detection of anti-p53 antibodies in former uranium miners (SDAG Wismut)

“…Also the mutations may re¯ect etiological contributions. Speci®c transversions (AGG b ATG) at codon 249 are described as a genotoxic effect and a marker for radon-associated lung cancer [Taylor et al, 1994], but other authors could not con®rm these hotspot mutations [Va Èha Èkangas et al, 1992;Bartsch et al, 1995]. Wang et al [1995] observed in 40% of lung cancer patients G:C to T:A transversion mutations in the p53 gene.…”

Analysis of radon-associated squamous cell carcinomas of the lung for a p53 gene hotspot mutation

“…With a larger database of p53 mutations in lung carcinoma in which details on histological subtype and patient exposure history are available, it would be possible to explore the still tenable hypothesis that the arg→met substitution at p53 residue 249, perhaps Taylor et al (1994) and McDonald et al (1995). Data from Bartsch et al (1995) and this report. *χinduced by oxidative damage from cigarette smoke and/or cytoplasmic damage from alpha-particle traversal, is preferentially selected for in bronchial squamous epithelium.…”

“…Reactions to amplify exon 7 of the p53 tumour suppressor gene were performed essentially as described previously (Bartsch et al, 1995). Reactions (50 µl) contained 2-4 µl of tumour DNA sample (an estimated 10-30 ng of DNA), and DNA was amplified with oligonucleotide primers specific for human p53 gene intron sequences flanking exon 7.…”

“…Tissue archives (hereafter referred to as the Stollberg Archive) containing tens of thousands of fixed tissue autopsy samples from employees of the Wismut mining company are being investigated now by pathologists and epidemiologists, and first results indicate that there is a high number of lung tumours in this Archive in comparison with pathology archives of non-mining areas in former East Germany. The first 50 lung tumours we screened from the Stollberg Archive revealed no arg→met hotspot mutations (Bartsch et al, 1995;Hollstein et al, 1997). In this initial study, nine of the 50 tumors were SCC.…”