van Maanen J M, Welle I J, Hageman G, Dallinga J W, Mertens P L, Kleinjans J C
Department of Health Risk Analysis and Toxicology, University of Limburg, Maastricht, The Netherlands.
Environ Health Perspect. 1996 May;104(5):522-8. doi: 10.1289/ehp.96104522.
We studied peripheral lymphocyte HPRT variant frequency and endogenous nitrosation in human populations exposed to various nitrate levels in their drinking water. Four test populations of women volunteers were compared. Low and medium tap water nitrate exposure groups (14 and 21 subjects) were using public water supplies with nitrate levels of 0.02 and 17.5 mg/l, respectively. Medium and high well water nitrate exposure groups (6 and 9 subjects) were using private water wells with mean nitrate levels of 25 and 135 mg/l, respectively. Higher nitrate intake by drinking water consumption resulted in a dose-dependent increase in 24-hr urinary nitrate excretion and in increased salivary nitrate and nitrite levels. The mean log variant frequency of peripheral lymphocytes was significantly higher in the medium well water exposure group than in the low and medium tap water exposure groups. An inverse correlation between peripheral lymphocyte labeling index and nitrate concentration of drinking water was observed. Analysis of N-nitrosamine in the urine of 22 subjects by gas chromatography-mass spectrometry revealed the presence of N-nitrosopyrrolidine in 18 subjects. Analysis of the mutagenicity of well water samples showed that a small number of the well water samples were mutagenic in the Ames Salmonella typhimurium test after concentration over XAD-2 resin. In conclusion, consumption of drinking water, especially well water, with high nitrate levels can imply a genotoxic risk for humans as indicated by increased HPRT variant frequencies and by endogenous formation of carcinogenic N-nitroso compounds from nitrate-derived nitrite.
我们研究了饮用水中硝酸盐含量各异的人群外周淋巴细胞次黄嘌呤磷酸核糖转移酶（HPRT）变异频率和内源性亚硝化作用。比较了四组女性志愿者受试人群。低硝酸盐暴露和中等硝酸盐暴露的自来水组（分别为14名和21名受试者）使用的公共供水硝酸盐含量分别为0.02毫克/升和17.5毫克/升。中等硝酸盐暴露和高硝酸盐暴露的井水组（分别为6名和9名受试者）使用的私人水井平均硝酸盐含量分别为25毫克/升和135毫克/升。通过饮用摄入更高的硝酸盐导致24小时尿硝酸盐排泄呈剂量依赖性增加，唾液硝酸盐和亚硝酸盐水平也升高。中等井水暴露组外周淋巴细胞的平均对数变异频率显著高于低硝酸盐暴露和中等硝酸盐暴露的自来水组。观察到外周淋巴细胞标记指数与饮用水硝酸盐浓度呈负相关。通过气相色谱-质谱法分析22名受试者尿液中的N-亚硝胺，发现18名受试者尿液中存在N-亚硝基吡咯烷。对井水样本的致突变性分析表明，少数井水样本经XAD-2树脂浓缩后在鼠伤寒沙门氏菌Ames试验中具有致突变性。总之，饮用高硝酸盐含量的水，尤其是井水，可能对人类具有遗传毒性风险，这表现为HPRT变异频率增加以及由硝酸盐衍生的亚硝酸盐内源性形成致癌性N-亚硝基化合物。
