SYNTHESIS AND MUTAGENICITY OF 4-(N-BUTYLNITROSAMINO)-4-HYDROXYBUTYRIC ACID LACTONE, A POSSIBLE ACTIVATED METABOLITE OF THE PROXIMATE BLADDER CARCINOGEN N-BUTYL-N-(3-CARBOXYPROPYL)NITROSAMINE
- 1 January 1980
- journal article
- research article
- Vol. 40 (1) , 162-165
Abstract
4-(N-Butylnitrosamino)-4-hydroxybutyric acid lactone (BBAL) was synthesized as a possible intermediate produced by metabolic activation of a selective bladder carcinogen, N-butyl-N-(3-carboxypropyl)nitrosamine. BBAL was stable in neutral sodium phosphate buffer (ionic strength, 0.2), with a half-life of more than 30 h at 25.degree.. The mutagenic effects of BBAL were tested with the use of Salmonella typhimurium TA1535 and Escherichia coli B/rWP2-try-, WP2-try-hcr-, and Sd4. The gene-damaging effects were assayed by repair tests with Bacillus subtilis H17 (rec+) and M45 (rec-). BBAL showed potent effects in the mutation and repair tests on all the strains without activation. A possibility is suggested for the metabolic activation of N-butyl-N-(3-carboxypropyl)-nitrosamine to BBAL by .alpha.-hydroxylation at the site of the 3-carboxypropyl chain followed by lactonization in target tissues prior to interaction with macromolecules to lead to carcinogenesis.This publication has 7 references indexed in Scilit:
- MUTAGENIC AND DNA-DAMAGING EFFECTS OF N-ALKYL-N-(ALPHA-ACETOXYALKYL)NITROSAMINES, MODELS FOR METABOLICALLY ACTIVATED N,N-DIALKYLNITROSAMINES1979
- STUDY OF CHEMICAL CARCINOGENESIS .6. EVIDENCE FOR METABOLIC ALPHA-HYDROXYLATION OF N-NITROSOPYRROLIDINE1978
- Syntheses of N-(.OMEGA.-acetoxyalkyl and .OMEGA.-carbomethoxyalkyl)-N-(.ALPHA.-acetoxyalkyl)nitrosamines, model compounds for possible metabolically activated N,N-dialkylnitrosamines.CHEMICAL & PHARMACEUTICAL BULLETIN, 1978
- Selective Induction of Intestinal Tumors in Rats by Methyl(acetoxymethyl)nitrosamine, an Ester of the Presumed Reactive Metabolite of Dimethylnitrosamine2JNCI Journal of the National Cancer Institute, 1977
- MUTAGENICITY OF N-BUTYL-N-(4-HYDROXYBUTYL)NITROSAMINE, A BLADDER CARCINOGEN, AND RELATED COMPOUNDS1977
- CARCINOGENICITY OF N-NITROSAMINES RELATED TO N-BUTYL-N-(4-HYDROXYBUTYL)NITROSAMINE AND N,N-DIBUTYLNITROSAMINE IN ACI-N RATS1976
- A Survey of Chemicals for Mutagenic Action on E. coliThe American Naturalist, 1951