Comparative study of tumorigenicity in mice administered transplacentally or neonatally with metabolites of tryptophan and its related compounds

Summary

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 tranplacentally for tumorigenicity. Animals treated were observed for 1 year.

Hepatocelluar 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.