Point mutation and DNA amplification studies on ras and myc gene in lung cancer

121 analog was investigated using repair deficient strains of Escherichia coli K12. Their mutagenic effect is strongly dependent on the excision repair pathway and is probably independent of the SOS error prone repair pathway. The direct involvement of DNA polymerase I or dam methylase in the mutagenic action of azidoglycerol has not been proved. It was also found that the induced mutations were predominantly AT-TA transversions. It seems that glycolysis plays a major role in the metabolic activation of azidoglycerol. Its mutagenicity is significantly influenced by the nature of the carbon source in the medium and by the aerobic or anaerobic growth conditions during its mutagenic action.

14 Hackman, P., K. Husgafvel-Pursiainen, S. Anttila, M. Ridanp~iii, A. Karjalainen and H. Vainio, Institute of Occupational Health, Helsinki (Finland) Point mutation and DNA amplification studies on r a s and m y c genes in lung cancers

We studied the mutational activation of K-ras oncogenes in lung cancer patients. Tumour samples from 36 patients have been screened for point mutations in the K-ras oncogene exon 1 codons 12 and 13. All of these patients were smokers or ex-smokers. Of the 36 lung carcinomas 17 were histologically squamous cell carcinomas, 16 adenocarcinomas and 3 small cell carcinomas. Fourteen of these patients had a history of occupational exposure to asbestos. Specific DNA sequences of the human K-ras oncogene exon 1 from the isolated DNA samples were amplified using the PCR technique and analysed for specific point mutations by dot-blot and oligoprobe techniques. Eleven tumour DNA samples showed point mutations reproducibly in codons 12 and 13. Genomic DNA from peripheral white blood cells from the same patients were negative. The DNA samples are also being analysed for amplifications of the ras and myc genes, using dot-blot techniques.

15 Hartwig, A., R.D. Snyder, U. Kasten, R. Schlepegrell and D. Beyersmann, Department of Biology and Chemistry, University of Bremen, D-2800 Bremen 33 (Germany) Direct and indirect mechanisms in cobalt genotoxicity in mammalian cells

While cobalt compounds are carcinogenic in experimental animals, the data concerning human exposure are still inconclusive. In bacterial mutagenicity test systems, cobalt(II) itself is inactive and exerts antimutagenic effects in combination with various chemical and physical agents. In mammalian cells, however, the responses are quite different: cobalt(II) induces DNA strand breaks in HeLa cells, a small increase in 6-thioguanine-resistant mutants and - more pronounced - sister-chromatid exchanges in V79 Chinese hamster cells. Additionally, it enhances the UV-induced genotoxicity at different endpoints in V79 cells. These modulating effects may be due to an increase of DNA repair: cobalt(II) inhibits the removal of UV-induced pyrimidine dimers and leads to an accumulation of DNA strand breaks during UV repair in HeLa cells, indicating an interference with either the polymerization or the ligation step in excision repair. Comparing the data from bacterial and mammalian test systems, the results point out the importance of using mammalian cells when assessing the toxicity of metal compounds.

16 Holme, J.A., C. Bjcrge, E.J. SOderlund, G. Brunborg, R. Becher, M, Lag, P. Schwarze, G. Nelson 1, j. Ross ~ and S. Nesnow 1, Institute of Public Health, Oslo (Norway) and ~EPA, esearch Triangle Park, NC 27711 (USA) Genotoxic effects of cyclopenta-fused polyaromatic hydrocarbons in isolated rodent liver and lung cells

Cyclopenta-fused polyaromatic hydrocarbons are a class of environmental PAH that have been recently identified. Many of these chemicals have