CARCINOGENESIS:In vivo formation of mutagens by intraperitoneal administration of polycyclic aromatic hydrocarbons in animals during exposure to nitrogen dioxide |
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| Authors: | Miyanishi Koichi; Kinouchi Takemi; Kataoka Keiko; Kanoh Takako; Ohnishi Yoshinari |
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| Institution: | Department of Bacteriology, School of Medicine, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770
1Department of Environmental Health, Tokyo Metropolitan Research Laboratory of Public Health, 3-24-1 Hyakunin-cho, Shinjuku-ku, Tokyo 160, Japan |
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| Abstract: | Consumption of fossil fuels has increased indoor and outdoorconcentrations of polycyclic aromatic hydrocarbons (PAHs) andnitrogen dioxide (NO2). To study the combined effect of PAHadministration and NO2 exposure on mutagenicity of urine fromanimals we injected 400 mg/kg body wt i.p. one of five kindsof PAH (pyrene, fluoranthene, fluorene, anthracene and chrysene)into ICR mice, Wistar rats, Syrian golden hamsters or Hartleyguinea pigs after exposure to 20 p.p.m. NO2 gas for 24 h andthen exposed the animals to NO2 gas for an additional 24 h.During the latter 24 h we collected the urine and assayed itsmutagenicity with the Ames Salmonella strains after treatmentwith ß-glucuronidase and arylsulfatase and extractionwith dichloromethane. The urine from mice treated with bothPAH and NO2 showed high mutagenicity for Salmonella typhimuriumstrains TA98 and TA100, whereas the urine from mice treatedwith PAH and air showed almost no mutagenic activity. The mutagenicitywas decreased in nitroreductase- and acetyltransferase-deficientstrains TA98NR and TA98/1, 8-DNP6 respectively. Treatment witha mixture of 20% of each of the five kinds of PAH and NO2 augmentedthe urinary mutagenicity of mice 1.5-fold. The urine from hamsterstreated with pyrene or fluoranthene and NO2 was also highlymutagenic, but that from rats or guinea pigs was not very mutagenic.The mutagenicity was also decreased in strains TA98NR and TA98/1,8-DNP6. These results suggest that the urine contains nitrocompounds and that the nitration of PAHs occurs in the bodyof animals under exposure to NO2 gas. Actually, the nitratedmetabolites of pyrene, l-nitro-6/8-hydroxypyrene and l-nitro-3-hydroxypyrene,were detected in the urine from mice treated with pyrene underexposure to NO2 gas. To elucidate the mechanism of in vivo nitration,NO2 (20 p.p.m.) was bubbled through 50 mM TVis-HCl buffer (pH7.4) or dichloromethane solution containing pyrene or 1-hydroxypyrene(10 µg/ml). Pyrene was not nitrated by NO2 in either aqueousor organic solutions. However, 1-hydroxypyrene was changed tonitrohydroxy-pyrenes by NO2 in the Tris-HCl buffer, but notin the organic solution. Ascorbic acid, |
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