Mutagenicity of Combined Treatment with Sodium Nitrite and Ascorbic Acid in Bacterial and Mammalian Cells

Genes and Environment

Masao Hirose²  Kyomu Matsumoto¹  Takanori Harada¹  Kunio Wada¹ 

[1] Laboratory of Genetic Toxicology, The Institute of Environmental Toxicology;Division of Pathology, National Institute of Health Sciences

关键词: sodium nitrite;    ascorbic acid;    combined treatment;    reverse mutation assay;    cytogenetic assay;   

DOI  :  10.3123/jemsge.30.10

学科分类：分子生物学，细胞生物学和基因

来源: Japanese Environmental Mutagen Society / Nihon Kankyo Hen igen Gakkai

【 摘 要 】

References(39)Cited-By(2)Simultaneous administration of sodium nitrite (NaNO2) and ascorbic acid (AsA) induces weak oxidative DNA damage in forestomach epithelium and enhances forestomach carcinogenesis in F344 rats. To investigate the mutagenicity of the combination of NaNO2 and AsA, we conducted reverse mutation assays in E. coli WP2uvrA/pKM101 and cytogenetic assays in cultured Chinese hamster lung CHL/IU cells without a metabolic activation system. When WP2uvrA/pKM101 was preincubated with a combination of 78.1-5000 μg/plate NaNO2 and 5 mg/plate AsA in standard buffer (pH 7.4), the number of revertants slightly increased compared to treatment with NaNO2 alone. Performing the same experiment using pH 6.0 buffer, in which the buffer decreased to about pH 4.9 due to the acidity of AsA, demonstrated that the number of revertants markedly increased. Additional experiments showed that the mutagenicity of NaNO2 itself markedly increased at pH 5.0-5.5. These results suggest that the enhancement of the mutagenic activity of NaNO2 in pH 6.0 buffer is likely due to a pH-lowering effect of AsA. In the cytogenetic assays, no substantial increase in chromosomally aberrant cells was observed in cultures treated with NaNO2 or AsA alone for 3 h, but combined treatment with 5 mg/mL NaNO2 and 1.5-2.5 mg/mL AsA significantly increased chromosome aberrations. We concluded that simultaneous treatment with NaNO2 and AsA at high doses induced mutagenic or clastogenic damage to bacterial and mammalian cells and that such genotoxic damage probably contributed to forestomach carcinogenesis in rats treated with combined NaNO2 and AsA.

【 授权许可】

Unknown