Determination of carcinogenic potential of mineral fibers by 8-hydroxydeoxyguanosine as a marker of oxidative DNA damage in mammalian cells.
8-Hydroxydeoxyguanosine (8-OH-dG) is a typical form of oxidative DNA damage, which causes mutations in vitro and in vivo. To develop a simple method of testing the carcinogenicity of fibrous materials, the formation of 8-OH-dG was determined in the DNA of J774 cells, an established reticulum cell sarcoma line, after treatment with various natural and man-made mineral fibers. The amount of 8-OH-dG was determined using high-pressure liquid chromatography (HPLC) equipped with an electrochemical detector (ECD). We tested three natural mineral fibers (crocidolite, amosite, and chrysotile) and three man-made mineral fibers (ceramic, glass, and potassium octatitanate). Among them, a significant increase in 8-OH-dG formation was observed in the crocidolite- and amosite-treated cells. We also measured the amount of tumor necrosis factor (TNF) produced by J774 cells incubated with the fibrous materials. Cellular TNF production increased after treatment with all the fibers tested, but it was not statistically significant except in the case of chrysotile. Therefore, these results indicate that the mechanism of TNF production is different from that of 8-OH-dG formation, and that the carcinogenicity of various fibrous materials can be better evaluated by measuring the 8-OH-dG level in J774 cellular DNA after treatment with these fibers.
Murata-Kamiya
N
N
Department of Health Policy and Management, University of Occupational and Environmental Health, Kitakyushu, Japan.
Tsutsui
T
T
Fujino
A
A
Kasai
H
H
Kaji
H
H
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001194:Asbestos / Q000009:adverse effects; D015415:Biomarkers; D015197:Carcinogenicity Tests; D002274:Carcinogens, Environmental; D002460:Cell Line; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives*; D005609:Free Radicals / Q000009:adverse effects; D066298:In Vitro Techniques; D019016:Mineral Fibers / Q000009:adverse effects*; D018384:Oxidative Stress; D012513:Sarcoma, Experimental; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D015415:Biomarkers; D002274:Carcinogens, Environmental; D005609:Free Radicals; D019016:Mineral Fibers; D014409:Tumor Necrosis Factor-alpha; D001194:Asbestos; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine