Lack of genotoxicity of the cancer chemopreventive agent N-(4-hydroxyphenyl)retinamide.
As part of the preclinical drug safety evaluation of the cancer chemopreventive agent N-(4-hydroxyphenyl)retinamide (HPR) in vitro and in vivo tests were conducted to assess its genotoxic activity. Negative findings from HPR testing were demonstrated in the Ames Salmonella/microsomal activation test, the L5178Y mouse lymphoma assay, and a rat bone marrow cytogenetics study. These data imply that HPR lacks the ability to induce point mutations or chromosomal aberrations, and is therefore not genotoxic. Limited testing of retinyl acetate in the Ames test, the L5178Y mouse lymphoma assay, and the primary rat hepatocyte/DNA repair assay yielded consistently negative results. These findings and previously published results concerning retinoid genotoxicity are discussed.
Paulson
J D
JD
Oldham
J W
JW
Preston
R F
RF
Newman
D
D
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001854:Bone Marrow Cells; D002869:Chromosome Aberrations; D006224:Cricetinae; D003582:Cytogenetics; D004224:Diterpenes; D017313:Fenretinide; D007940:Leukemia L5178 / Q000235:genetics / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D009152:Mutagenicity Tests; D051381:Rats; D012176:Retinoids / Q000633:toxicity; D000084562:Retinyl Esters; D012486:Salmonella typhimurium / Q000235:genetics; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000633:toxicity; D014801:Vitamin A / Q000031:analogs & derivatives / Q000633:toxicity
D000970:Antineoplastic Agents; D004224:Diterpenes; D012176:Retinoids; D000084562:Retinyl Esters; D014801:Vitamin A; D017313:Fenretinide; C009166:retinol acetate; D014212:Tretinoin