Mutagenicity of hydroxamic acids and the probable involvement of carbamoylation.
A series of hydroxamic acids (aceto-, propiono-, benzo-, and p-nitrobenzo-) and seven derivatives of these were examined for biological activity using Salmonella typhimurium. Acylation to yield O-acetyl and O-benzoyl derivatives markedly enhanced toxic properties and was necessary for mutagenic activity for all but p-nitrobenzohydroxamic acid. The dose necessary to produce a minimum significant mutagenic response varied from 21 microM for O-benzoyl benzohydroxamate to 430 microM for O-acetyl acetohydroxamate. These two compounds were also tested with human lymphoblasts to which they were toxic at 100 microM but not mutagenic. O-Acetyl benzohydroxamate, a mutagen, was prepared wih a 14C label in the carbonyl carbon atom of the benzoyl group and was shown to form an adduct in vitro with DNA and polyguanylic acid. The level of binding was 1 mol of 14C per 5 X 10(4) mol of DNA phosphate and 1 mol of 14C per 10(5) mol of polyguanylic acid phosphate.
D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects; D009153:Mutagens; D011068:Poly G / Q000378:metabolism; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D006877:Hydroxamic Acids; D009153:Mutagens; D011068:Poly G; D004247:DNA