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Combination effect of citrinin and other chemicals on rat kidney tumorigenesis
Abstract:
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.
Insights
Citrinin combined with N-nitrosodimethylamine (DMN) significantly increases kidney tumor incidence and alters tumor type in rats. Citrinin also enhances NDPS-induced kidney tumors, confirming its role in chemical carcinogenesis.
Area of Science:
- Toxicology
- Carcinogenesis
- Histopathology
Background:
- Citrinin is a nephrotoxic mycotoxin.
- N-(3,5-dichlorophenyl)succinimide (NDPS) and N-nitrosodimethylamine (DMN) are known nephrotoxic chemicals.
Purpose of the Study:
- To investigate the nephrotoxic and carcinogenic effects of citrinin, alone and in combination with NDPS and DMN, on rat kidneys.
- To determine how citrinin modifies the histological type and incidence of kidney tumors induced by DMN and NDPS.
Main Methods:
- Rats were orally administered citrinin alone, DMN alone, NDPS alone, or combinations of citrinin with DMN or NDPS.
- Kidney tissues were examined histologically to assess toxicity and identify tumor types.
Main Results:
- Citrinin alone caused kidney injury but no tumors.
- DMN alone induced kidney tumors in 57.1% of rats.
- Citrinin combined with DMN significantly increased kidney tumor incidence (94.7% and 86.7%) and altered tumor types, favoring renal cell tumors.
- Citrinin combined with NDPS induced kidney tumors (22.2%) in rats, which were histologically renal cell tumors (adenomas).
Conclusions:
- Citrinin acts as a co-carcinogen, modifying the incidence and histological type of kidney tumors induced by DMN.
- Citrinin in combination with NDPS can induce renal cell tumors in rats.