Mereto E, Brambilla Campart G, Ghia M, Petrogalli F
Institute of General Pathology, University of Genoa, Italy.
Cancer Lett. 1990 Aug;53(1):61-5. doi: 10.1016/0304-3835(90)90011-l.
Chlordiazepoxide (CDE) reacts with sodium nitrite at acid pH yielding the genotoxic derivative N-nitrosochlordiazepoxide (NO-CDE). In the present study oral administration of CDE plus NaNO2, previously found to produce DNA fragmentation in the rat liver, was examined for its ability to initiate hepatocarcinogenesis. The oral treatment for 6 successive weeks with CDE + NaNO2, added to the diet at the levels of 290 + 270 and 870 + 800 ppm, did not significantly increase the number or volume of gamma-glutamyltranspeptidase-positive foci (putative preneoplastic lesions). These findings are in agreement with the negative results previously obtained in rodent carcinogenesis assays and indicate that NO-CDE belongs to the progressively expanding list of genotoxic non-carcinogens.
氯氮卓（CDE）在酸性pH条件下与亚硝酸钠反应生成遗传毒性衍生物N-亚硝基氯氮卓（NO-CDE）。在本研究中，对先前发现可在大鼠肝脏中产生DNA片段化的CDE加NaNO₂进行口服给药，检测其引发肝癌发生的能力。以290 + 270和870 + 800 ppm的水平添加到饮食中，连续6周口服CDE + NaNO₂，并未显著增加γ-谷氨酰转肽酶阳性灶（假定的癌前病变）的数量或体积。这些发现与先前在啮齿动物致癌试验中获得的阴性结果一致，表明NO-CDE属于遗传毒性非致癌物这一逐渐扩大的类别。
