Role of nitrosation in the mutagenic activity of coal dust: a postulation for gastric carcinogenesis in coal miners

The mutagenicity of coal dust solvent extracts with and without nitrosation was studied using the Salmonella/microsome assay system. Coal dust solvent extracts were either non-mutagenic or very weakly mutagenic with S9 activation. High mutagenic activities, however, were found when extracts of bituminous, subbituminous, and lignite coal dusts were reacted with nitrite under an acidic condition. Formation of mutagens from coal dust extracts by nitrosation was highest at pH 3.2 and decreased with increasing pH in the reaction mixture. Mutagenic activity appeared to be independent of metabolic activation. The mutagens formed from nitrosation of coal dust extracts induced frameshift mutations. The results reported here may have possible implications for the explanation of an elevated incidence of gastric cancer in coal miners.     

The urine mutagenicity assay system. Studies related to recovery, storage and concentration procedures

Studies were conducted to determine (i) the effect of storage on the mutagenic activity of urine spiked with known mutagens, (ii) the efficiency of XAD-2 column on the recovery of complex mixtures from spiked urine samples, and (iii) whether the addition of XAD-7 resin to the column and/or the addition of methylene chloride to the elution process increases the recovery of mutagens from urine samples spiked with complex mixtures. Chemically spiked or nonspiked urine samples were concentrated with XAD resin and were tested for mutagenic activity with the Ames Salmonella/microsome assay system. The results indicate that the mutagenic activity of chemically spiked urine remains essentially unchanged after 7 d, but it decreases by approximately 50% for some compounds after 28 d of storage at -70 degrees C. The recovery of mutagens from mutagen-spiked urine varied from 0% to more than 100%. Mutagenic activities of concentrates from urine samples spiked with complex mixtures were higher if resin columns were eluted with both methylene chloride and acetone than with acetone alone. A slight increase in mutagenic activity was also found if a mixture of XAD-2 and XAD-7 instead of XAD-2 alone was used to concentrate urine spiked with air particle extracts.     

Role of nitrosation in the mutagenic activity of coal dust: A postulation for gastric carcinogenesis in coal miners

The mutagenicity of coal dust solvent extracts with and without nitrosation was studied using the Salmonella/microsome assay system. Coal dust solvent extracts were either non-mutagenic or very weakly mutagenic with S9 activation. High mutagenic activities, however, were found when extracts of bituminous, subbituminous, and lignite coal dusts were reacted with nitrite under an acidic condition. Formation of mutagens from coal dust extracts by nitrosation was highest at pH 3.2 and decreased with increasing pH in the reaction mixture. Mutagenic activity appeared to be independent of metabolic activation. The mutagens formed from nitrosation of coal dust extracts induced frameshift mutations. The results reported here may have possible implications for the explanation of an elevated incidence of gastric cancer in coal miners.     

Genetic effects of PR toxin in eukaryotic microorganisms.

The genetic activity of PR toxin, a mycotoxin from Penicillium roqueforti, was studied in Saccharomyces cerevisiae and Neurospora crassa. The results show that PR toxin, without enzymic activation, causes gene conversion in S. cerevisiae strains D4 and D7, reverse mutation in S. cerevisiae strain D7 and N. crassa strain N24, and mitotic crossing-over in S. cerevisiae strain D7, In the log phase cells of S. cerevisiae the effects are more pronounced at alkaline than at acid pH. The active site responsible for the genetic activity and toxicity is known. The carbonyl groups appear to play an important role in the biologic activity of this molecule.     

Gastric cancer in coal miners: an hypothesis of coal mine dust causation

An hypothesis is proposed to explain the elevated incidence of gastric cancer among coal miners. Inhaled coal mine dust, especially the larger particles, is cleared from the lung and tracheobronchial tree by mucociliary function, swallowed, and introduced into the stomach. Organic and/or inorganic materials in the dust can undergo intra-gastric nitrosation and/or interaction with exogenous chemicals to form carcinogenic compounds which in turn may lead to precancerous lesions, which may subsequently develop into gastric cancer. This sequence of events, however, depends upon occupational exposures as well as life-style features and individual genetic predisposition.     

Application of SOS umu-test for the detection of genotoxic volatile chemicals and air pollutants

The SOS umu-test has been used for the detection of DNA-damaging agents. In this system the plasmid pSK1002 carrying a fused gene umuC-lacZ was introduced into Salmonella typhimurium TA1535. The SOS function induced by genotoxic agents is detected by a colorimetric measurement of beta-galactosidase activity encoded by the lacZ gene, which is regulated by the Umu operon. This system was used with modifications to study the SOS function inducibility of volatile chemicals (propylene oxide, methyl bromide, and ethylene dibromide) and air pollutants (diesel emission, welding fumes, and cigarette smoke). Tester cells were exposed directly to the test material. The enzyme activity of the treated cells was measured according to the established procedure. Results of the study showed that all chemicals and pollutants tested induced SOS function in a dose-related manner. These results indicate that the SOS umu-test is potentially useful for the in situ detection of genotoxic agents in occupational settings.     

Induction of micronuclei in cultured mammalian cells by fume condensates of roofing asphalt

A considerable number of workers in the United States are employed in asphalt industries and are potentially exposed to asphalt fumes. The information regarding the potential carcinogenic hazards of such fumes to exposed workers is still limited. Studies have been conducted to determine the cytogenetic effects of roofing asphalt fume using cultured mammalian cells. Exponentially growing Chinese hamster lung fibroblasts (V79 cells) were exposed to different concentrations of condensates of type I and type III roofing asphalt fumes, generated at temperatures similar to actual roofing operation (316 ± 10°C). The frequencies of micronucleated cells in the treated and control cultures were determined. Additionally, immunofluorescent staining of kinetochore with human anti-kinetochore primary antibody and flouresceinated goat anti-human IgG was used to investigate the potential mechanism of micronucleus formation. The results show that both types of roofing asphalt fume condensates caused a significant increase in the frequency of micronucleated cells, and that 70% of micronucleated cells induced by asphalt fume condensates carried kinetochore-positive micronuclei. These findings indicate that both type I and type III roofing asphalt fumes are capable of causing principally cytogenetic damage by spindle apparatus alternations in cultured mammalian cells. © 1996 Wiley-Liss, Inc.