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Title: Mutagenicity of N- and O-acetyl derivatives of methyl 3,4-diphenyl-5-hydroxylamino-2-furoate and n-hydroxy-4-aminobiphenyl in Salmonella typhimurium

Methyl 3,4-diphenyl-5-hydroxylamino-2-furoate (N-OH-MDPF) (I), methyl 3,4-diphenyl-5-acetoxyamino-2-furoate (N-OAc-MDPF) (II), methyl 3,4-diphenyl-N-hydroxy-5-acetylamino-2-furoate (N-OH-MDPAF) (III), and methyl 3,4-diphenyl-N-acetoxy-5-acetylamino-2-furoate (N-OAc-MDPAF) (IV) were synthesized and tested for mutagenic activity for Salmonella typhimurium TA98 and TA100. The hydroxylamine (I) and acetyl derivatives (II - IV) did not show mutagenic activity in TA98 or TA100. In contrast, the parent nitro compound, methyl 3,4-diphenyl-5-nitro-2-furoate (MDPNF) (V) was found to be equally active in TA98 and TA98-DNP, and more active in TA100 and TA104. The mutagenic activity in TA100 and TA104 decreased significantly under anaerobic conditions. These data suggest that mechanisms involving O-acetylation of N-hydroxylamine to the acetoxyamine or acyl transfer reactions are not involved in the generation of mutagen from MDPNF. Furthermore, the differential mutagenic response of V in TA98 and TA98NR, its reduction to I, and the lack of activity of I suggest that the intermediates of reduction between the nitro and hydroxylamine, such as nitro or nitroso free radical anions, may be involved in mutagenesis. The decreased response of V under anaerobic conditions and increased response in TA104 suggest that secondary oxygen radicals generated from reduction intermediates may be responsible for the mutagenicity of MDPNF.
Authors:
; ;  [1] ; ;  [2] ;  [3]
  1. (Univ. of Wisconsin, Madison (United States))
  2. (Josai Univ., Saitama (Japan))
  3. (Nagasaki Univ. Hospitals (Japan))
Publication Date:
OSTI Identifier:
6097926
Resource Type:
Journal Article
Resource Relation:
Journal Name: Environmental and Molecular Mutagenesis; (United States); Journal Volume: 17:2
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; FURANS; DERIVATIZATION; HETEROCYCLIC COMPOUNDS; MUTAGEN SCREENING; REVERTANTS; MUTATION FREQUENCY; ANAEROBIC CONDITIONS; BIPHENYL; HYDROXYLAMINE; METABOLIC ACTIVATION; POLYCYCLIC NITRO COMPOUNDS; SALMONELLA TYPHIMURIUM; TRANSFERASES; AMINES; AROMATICS; BACTERIA; CHEMICAL REACTIONS; ENZYMES; HYDROCARBONS; MICROORGANISMS; MUTANTS; NITRO COMPOUNDS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANIC OXYGEN COMPOUNDS; PROTEINS; SALMONELLA; SCREENING 560300* -- Chemicals Metabolism & Toxicology