Metabolism and <i>in vitro</i> assessment of the mutagenic activity of urinary extracts from rats after inhalation exposure to 1-methylnaphthalene

微核试验 吸入 化学 微核 CYP1A2 吸入染毒 尿 排泄 致癌物 新陈代谢 仓鼠 泌尿系统 毒性 内分泌学 内科学 药理学 细胞色素P450 生物化学 生物 医学 麻醉 有机化学
作者
Radosław Świercz,Maciej Stępnik,Jolanta Gromadzińska,Katarzyna Domeradzka-Gajda,Joanna Roszak,Wojciech Wąsowicz
出处
期刊:International Journal of Occupational Medicine and Environmental Health [Nofer Institute of Occupational Medicine]
卷期号:35 (6): 731-746
标识
DOI:10.13075/ijomeh.1896.01955
摘要

1-Methylnaphthalene (1-MN) is composed of 2 benzene rings and belongs to polycyclic aromatic hydrocarbons. The metabolism of 1-MN in laboratory animals and bacteria leads to the formation of 1-naphthoic acid (1-NA).In this study the distribution of 1-NA in lung, liver, spleen, kidney and urinary excretion of 1-NA in rats after single and repeated inhalation exposure to 1-MN vapors were investigated. The activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and cytochrome were measured of the rats. Genotoxic effects were evaluated with the in vitro micronucleus test on V79 hamster fibroblasts.The concentrations of 1-NA in the tissues of rats after single and repeated exposure to 1-MN were dependent on the exposure dose. High levels of 1-NA were found in kidneys of animals after the single and repeated exposure to 1-MN. With an increase of 1-MN dose, an increase in the activity of cytochrome P450 (CYP1A1 and CYP1A2) was observed in the liver of rats. Compared to control animals, significantly higher ALT activity was noted in serum of rats exposed to 1-MN. The micronuclei frequency in V79 cells exposed to 1-MN (in the range of analyzable concentrations; i.e., 5-25 μg/ml) did not differ significantly from the vehicle control, whereas urine extracts from rats exposed to 1-MN induced a significant increase in the frequency of micronuclei compared to urine extracts from the group of control animals.Metabolism of 1-MN in rats after the inhalation exposure leading to 1-NA was mainly observed during the first day after the end of exposure. It is likely that 1-MN metabolites present in rat urine can induce the increased micronuclei frequency as was shown in V79 cells. Int J Occup Med Environ Health. 2022;35(6):731-46.

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