Interferon induction inhibition and mutagenic activity of nitrosated coal dust extract.
Specified cytotoxicity and mutagenicity of coal dust extract (mixture of solvent extractions of bituminous coal nitrosated by NaNO2) were investigated because of the association of an excess risk of gastric cancer in coal miners. The effect of nitrosated coal dust on a cellular defense component of the interferon system, the induction of interferon (alpha/beta) in mammalian cell cultures by influenza virus, and mutagenicity, using the Salmonella/microsome assay, were determined. Nitrosated coal dust extract contained both bioactivation-independent and -dependent (microsome enzymatic activation) compounds that significantly inhibited the viral induction of interferon by greater than 50%. Nitrosated extract was mutagenic but exhibited no increase in mutagenic activity in the presence of microsomal enzymes. With further extraction of nitrosated coal dust extract by horse serum and fractionation thereof, the soluble chemical complexes formed with fractions of high molecular weight without bioactivation were dominant in both mutagenicity and inhibition of interferon induction. Low-molecular-weight fractions, with or without a metal chelator, and with or without bioactivation, all inhibited interferon induction comparably and significantly. There was no mutagenic activity manifested by these serum fractions. Metal-serum complexes were either not formed, or, if present, were ineffectual according to the biologic criteria employed. The findings of this study are discussed in terms of the association between nitrosated coal dust and gastric carcinogenesis.
D000818:Animals; D003031:Coal / Q000009:adverse effects*; D004391:Dust / Q000009:adverse effects*; D004492:Edetic Acid / Q000494:pharmacology; D006736:Horses / Q000097:blood; D007372:Interferons / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D009153:Mutagens / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000009:adverse effects*; D009975:Orthomyxoviridae / Q000502:physiology
D003031:Coal; D004391:Dust; D009153:Mutagens; D009603:Nitroso Compounds; D007372:Interferons; D004492:Edetic Acid