Oral administration of chlordiazepoxide plus sodium nitrite investigated for tumor initiating activity in the rat liver.

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.