Histological studies were made on the nephrotoxic effect of
citrinin on the kidneys of rats, with or without previous treatment with the nephrotoxic chemicals,
N-(3,5-dichlorophenyl)succinimide (
NDPS) and
N-nitrosodimethylamine (DMN).
Oral administration of 0.02% or 0.05%
citrinin alone caused signs of kidney injury but did not induce kidney
tumors. On treatment with DMN alone, 8 of 14 rats (57.1%) developed kidney
tumors; two (14.3%) were renal cell
tumors, eight (57.1%) embryonal cell
tumors, and one (7.1%)
hemangioendothelioma. On the other hand, kidney
tumors developed in 18 of 19 rats (94.7%) and 13 of 15 rats (86.7%) by the administration of 0.02% and 0.05%
citrinin, respectively, after DMN. The
tumors in these two groups were diagnosed histologically as renal cell
tumors in 18 (94.7%) in group IV and 13 (86.7%) in group III, and as embryonal cell
tumors in 14 (73.7%) in group IV and 9 (60.0%) in group III. Thus, in groups treated with
citrinin after DMN the incidence of renal cell
tumors was much greater and the incidence of embryonal cell
tumors slightly greater than in the group treated with DMN alone. Kidney
tumors developed in 4 of 18 rats (22.2%) treated with 0.02%
citrinin after
NDPS, but treatment with
NDPS alone did not induce kidney
tumors. Thus, treatment with
citrinin changes the histological type and incidence of kidney
tumors in rats induced by DMN. Moreover, this study confirms that
citrinin in combination with
NDPS can induce kidney
tumor in rats, which was renal cell
tumor (
adenoma) histologically.