Haloacetonitriles: metabolism, genotoxicity, and tumor-initiating activity
| Autor: | F B Daniel, S L Herren-Freund, Michael A. Pereira, E L Lin |
|---|---|
| Rok vydání: | 1986 |
| Předmět: |
Acetonitriles
Alkylation Health Toxicology and Mutagenesis Polynucleotides chemistry.chemical_element In Vitro Techniques Pharmacology medicine.disease_cause polycyclic compounds medicine Chlorine Animals Humans Hydrogen compounds Water contaminants Mutagenicity Tests Public Health Environmental and Occupational Health Cytochrome P-450 CYP2E1 Oxidoreductases N-Demethylating DNA Metabolism Biological materials Rats Biochemistry chemistry Peptide Hydrolases Toxicity Carcinogens Genotoxicity DNA Damage Mutagens Research Article |
| Zdroj: | Environmental Health Perspectives |
| ISSN: | 1552-9924 0091-6765 |
| DOI: | 10.1289/ehp.866967 |
| Popis: | Haloacetonitriles (HAN) are drinking water contaminants produced during chlorine disinfection. This paper evaluates metabolism, genotoxicity, and tumor-initiating activity of these chemicals. The alkylating potential of the HAN to react with the electrophile-trapping agent, 4-(p-nitrobenzyl)pyridine, followed the order dibromoacetonitrile (DBAN) greater than bromochloroacetonitrile (BCAN) greater than chloroacetonitrile (CAN) greater than dichloroacetonitrile (DCAN) greater than trichloroacetonitrile (TCAN). When administered orally to rats, the HAN were metabolized to cyanide and excreted in the urine as thiocyanate. The extent of thiocyanate excretion was CAN greater than BCAN greater than DCAN greater than DBAN much greater than TCAN. Haloacetonitriles inhibited in vitro microsomal dimethylnitrosamine demethylase (DMN-DM) activity. The most potent inhibitors were DBAN and BCAN, with Ki = 3-4 X 10(-5) M; the next potent were DCAN and TCAN, with Ki = 2 X 10(-4) M; and the least potent inhibitor was CAN, with Ki = 9 X 10(-2) M. When administered orally, TCAN, but not DBAN, inhibited hepatic DMN-DM activity. The HAN produced DNA strand breaks in cultured human lymphoblastic (CCRF-CEM) cells. TCAN was the most potent DNA strand breaker, and BCAN greater than DBAN greater than DCAN greater than CAN, which was only marginally active. DCAN reacted with polyadenylic acid and DNA to form adducts in a cell-free system; however, the oral administration of DBAN or DCAN to rats did not result in detectable adduct formation in liver DNA. None of the HAN initiated gamma-glutamyltranspeptidase (GGT) foci when assayed for tumor-initiating activity in rat liver foci bioassay.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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