title: Influence of functional group substitutions on the carcinogenicity of anthraquinone in rats and mice: analysis of long-term bioassays by the National Cancer Institute and the National Toxicology Program.
abstract: The carcinogenic activities of anthraquinone and six derivatives were compared and contrasted. Studies included representatives of amino, alkyl, nitro, hydroxy, or halogen-containing anthraquinones, with the purpose of uncovering general structure-activity relationships. Anthraquinone, 2-aminoanthraquinone, 1-amino-2-methylanthraquinone, 2-methyl-1-nitroanthraquinone,1-amino-2,4-dibromoanthraquinone, 1,4,5,8-tetraaminoanthraquinone, and 1,3,8-trihydroxy-6-methylanthraquinone (of varying purities) were administered via feed to Fischer 344/N rats and B6C3F, mice. In rats, anthraquinone induced tumors in the liver, kidney, and urinary bladder. A 2-amino substitution narrowed the carcinogenicity to the liver, while multiple amino substitutions led to a carcinogenic response in the urinary bladder alone. A methyl substitution ortho to a 1-aminogroup preserved the hepatic and renal neoplasms seen with the parent anthraquinone, but did not induce urinary bladder tumors; amino or bromo substitutions para to a 1-amino group were related to urinary bladder neoplasms. The intestine may have been a target organ for bromine-substituted anthraquinones. The presence of a nitro group altered the targets of carcinogenicity, and skin tumors may have been associated with this particular functional group in both rats and mice. Over-all for mice, the findings were somewhat different and limited by the small number of common target organs. The parent anthraquinone was clearly carcinogenic only to the liver. There were no other effects of single amino substitutions, in the presence or absence of an additional methyl group, on the carcinogenicity or the site of carcinogenesis of anthraquinone in mice. Multiple amino substitutions diminished, while bromine substitutions enhanced the carcinogenicity induced by anthraquinone and extended the target organs to include forestomach and lung.
authors.affiliation: National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. doi@niehs.nih.gov
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Doi
authors.forename: Richard D
authors.initials: RD
authors.lastname: Irwin
authors.forename: John R
authors.initials: JR
authors.lastname: Bucher
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000378:metabolism / Q000633:toxicity*; D001681:Biological Assay; D002273:Carcinogens / Q000633:toxicity*; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000880:Anthraquinones; D002273:Carcinogens