title: Mutagenicity and antimutagenicity studies of DRDE-07 and its analogs against sulfur mustard in the in vitro Ames Salmonella/microsome assay.
abstract: Sulfur mustard (bis(2-chloroethyl) sulfide, SM), a chemical warfare agent, is classified as a class I human carcinogen by IARC. No effective antidote against this agent is available. The synthetic aminothiol, amifostine, earlier known as WR-2721, has been extensively used as a chemical radioprotector for normal tissues in cancer radiotherapy and chemotherapy. SM is a radiomimetic agent; this prompted us to evaluate the protective efficacy of amifostine and three of its analogs, DRDE-07 [S-2(2-aminoethylamino) ethyl phenyl sulphide], DRDE-30 [S-2(2-aminoethyl amino) ethyl propyl sulphide] and DRDE-35 [S-2(2-aminoethyl amino) ethyl butyl sulphide], against sulfur mustard-induced mutagenicity in the Ames Salmonella/microsome assay. The antidotes were also evaluated for possible mutagenic activity. DRDE-07 was mutagenic in strain TA104 in the absence of S9; DRDE-30 was mutagenic in strain TA100; amifostine and DRDE-35 did not show mutagenic activity in any of the five tester strains used. SM is mutagenic in strains TA97a and TA102, with or without S9 activation. In the antimutagenicity studies, DRDE-07 and DRDE-35 showed promising antimutagenic activity against SM in the absence of S9, in comparison to amifostine. DRDE-07 and DRDE-35 are promising protective agents against SM-induced mutagenicity.
authors.affiliation: Regulatory Toxicology Division, Defence Research and Development Establishment, Jhansi Road, Gwalior 474 002, India. Electronic address: vinodvk@drde.drdo.in.
authors.forename: Vinod
authors.initials: V
authors.lastname: Vijayan
authors.affiliation: Synthetic Chemistry Division, Defence Research and Development Establishment, Jhansi Road, Gwalior 474 002, India.
authors.forename: Uma
authors.initials: U
authors.lastname: Pathak
authors.affiliation: Microbiology Division, Defence Research and Development Establishment, Jhansi Road, Gwalior 474 002, India.
authors.forename: Ghansham Pundilikji
authors.initials: GP
authors.lastname: Meshram
mesh_terms: D004999:Amifostine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016587:Antimutagenic Agents / Q000494:pharmacology*; D002619:Chemical Warfare Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008861:Microsomes; D009151:Mustard Gas / Q000633:toxicity*; D009152:Mutagenicity Tests / Q000379:methods; D012486:Salmonella typhimurium
chemical_list: D016587:Antimutagenic Agents; D002619:Chemical Warfare Agents; C438646:S-2 (2-aminoethylamino)ethylphenylsulfide; D004999:Amifostine; D009151:Mustard Gas
keywords: Ames test; Amifostine; Antimutagenicity; DRDE-07; Mutagenicity; Sulfur mustard