Perspectives on the mechanism of action of the splenic toxicity of aniline and structurally-related compounds.
Aniline and several structurally-related aromatic amines produce spleen tumours in rats given high doses of compound in 2-year bioassay studies. Evaluation of the pathogenesis of the splenic lesions and characterization of the disposition of radiolabelled aniline in animals suggests that the spleen tumours may be a secondary response resulting from chemically-mediated erythrocyte toxicity. It is proposed that compound-derived toxicity to erythrocytes results in scavenging of damaged red blood cells by the spleen, initiating a series of events which may contribute to the development of spleen tumours. These events potentially include (i) specific accumulation of the parent compound or toxic metabolite(s) carried to the spleen by erythrocytes; (ii) deposition of erythrocytic debris, particularly iron, which may catalyse tissue-damaging free-radical reactions; and (iii) induction of splenic hyperplasia resulting from erythrocyte overload. Linkage of the splenic tumorigenicity of these aromatic amines to an initial toxic event in the erythrocyte suggests that the carcinogenicity of such compounds may be determined by a definable threshold dose, i.e. the events leading to the carcinogenicity are not initiated until the capacity of the red blood cell to cope with the toxic insult is exceeded.
Bus
J S
JS
Popp
J A
JA
D000814:Aniline Compounds / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006485:Hemosiderin / Q000378:metabolism; D008297:Male; D009153:Mutagens; D012737:Sex Factors; D013045:Species Specificity; D013158:Splenic Diseases / Q000139:chemically induced*; D013160:Splenic Neoplasms / Q000139:chemically induced
D000814:Aniline Compounds; D009153:Mutagens; D006485:Hemosiderin; C023650:aniline