Comparative study of tumorigenicity in mice administered transplacentally or neonatally with metabolites of tryptophan and its related compounds.
Intermediate metabolites of tryptophan, 3-hydroxy-L-kynurenine (3-OHKY), 3-hydroxyanthranilic acid (3-OHAA) and anthranilic acid (AA), and an enzyme inhibitor from 3-OHKY to 3-OHAA, isonicotinic acid hydrazide (INH) with or without 3-OHKY at the maximum tolerated dose were injected s.c. to infant CDF1 mice. AA and 3-OHAA were tested transplacentally for tumorigenicity. Animals treated were observed for 1 year. Hepatocellular adenoma was developed at the incidence of 21.7% in male mice administered with 3-OHKY and INH as compared with 5.6% incidence in control males, but no leukemia was induced. Incidences of lung (3.4--15.0%) and liver tumors (4--5%) in other groups treated at infant stage were comparable to that in controls (lung: 11.1%; liver: 5.6%). Other tumors were one angiogenic sarcoma in a female treated with 3-OHAA, and one granulosa cell tumor of ovary in female treated with INH. Transplacentally the 10.3% incidence of liver tumor in male offspring, whose mothers were treated with AA, was slightly higher than that in male control (5.6%). However, the incidences of tumor were apparently in a critical level in these experimental conditions.
D015095:3-Hydroxyanthranilic Acid / Q000378:metabolism / Q000633:toxicity; D000236:Adenoma / Q000139:chemically induced*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced*; D005260:Female; D006106:Granulosa Cell Tumor / Q000139:chemically induced; D006394:Hemangiosarcoma / Q000139:chemically induced; D007538:Isoniazid / Q000378:metabolism / Q000633:toxicity; D007737:Kynurenine / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity; D008113:Liver Neoplasms / Q000139:chemically induced*; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D010051:Ovarian Neoplasms / Q000139:chemically induced; D011247:Pregnancy; D062367:ortho-Aminobenzoates / Q000378:metabolism / Q000633:toxicity
D002273:Carcinogens; D062367:ortho-Aminobenzoates; D015095:3-Hydroxyanthranilic Acid; C005045:3-hydroxykynurenine; D007737:Kynurenine; D007538:Isoniazid