Oral administration of chlordiazepoxide plus sodium nitrite investigated for tumor initiating activity in the rat liver
Abstract
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.
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Early studies suggested continuous feeding of high milligram doses of sodium nitrite could facilitate the development of tumors.
“Early studies suggested that continuous feeding of high milligram doses of sodium nitrite could facilitate the development of tumors [269–271].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [269]
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Inorganic nitrite therapy: historical perspective and future directions
Kevil, C. G., Kolluru, G. K., Pattillo, C. B., & Giordano, T. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.04.042 · Cited by 113 · see citing works
- Authors
- Mereto, E., Brambilla Campart, G., Ghia, M., & Petrogalli, F.
- Affiliations
- University of Genoa (IT)
- Corresponding author
- Mereto, E.
- Venue
- Cancer Letters
- Publisher
- Elsevier BV
- Published
- 1990-08
- Volume
- 53
- Issue
- 1
- Pages
- 61-65
- ISSN
- 0304-3835 (ISSN-L)
- OpenAlex
- W2056157819
- Cited by
- 5
- References
- 19
- Citations by year
- 2018: 1 · 2017: 1
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Consiglio Nazionale delle Ricerche
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- chlordiazepoxide, sodium nitrite, hepatocarcinogenesis, tumor initiation, DNA fragmentation, precancerous lesions, rat liver, oral administration
- MeSH terms
- Administration, Oral, Animals, Chlordiazepoxide, Hepatectomy, Liver, Liver Neoplasms, Experimental, Male, Nitrites, Rats, Inbred Strains, Sodium Nitrite, Carcinogenicity Tests, Rats
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