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Fumonisins--novel mycotoxins with cancer-promoting activity produced by Fusarium moniliforme
W C Gelderblom1, K Jaskiewicz, W F Marasas
1Research Institute for Nutritional Diseases, South African Medical Research Council, Tygerberg.
Abstract:
Cultures on corn of Fusarium moniliforme MRC 826 are known to cause leukoencephalomalacia in horses and to be toxic and hepatocarcinogenic in rats. Culture material of this F. moniliforme isolate has also been shown to exhibit cancer-promoting activity in a short-term cancer initiation-promotion bioassay with diethylnitrosamine-initiated rats and the induction of gamma-glutamyl-transpeptidase-positive (GGT+) foci as an endpoint after 4 weeks of promotion. This bioassay was used as a monitoring system to isolate cancer-promoting compounds from cultures of F. moniliforme MRC 826. Culture material was successively extracted with ethyl acetate and CH3OH-H2O (3:1). Most of the cancer-promoting activity was recovered in the CH3OH-H2O extract and remained in the aqueous phase following partitioning of this extract between CH3OH-H2O (1:3) and CHCl3. The CH3OH-H2O fraction was chromatographed on an Amberlite XAD-2 column, and the active fraction was eluted with CH3OH. This fraction was chromatographed on a silica gel column with CHCl3-CH3OH-CH3COOH (6:3:1) as eluent and further purified on a C18 reverse-phase column. Two pure compounds were isolated, and these have been chemically characterized and given the trivial names fumonisin B1 and B2. At least 2 g of the major compound fumonisin B1 was purified from 1 kg of culture material. Fumonisin B1 in the diet (0.1%) significantly (P less than 0.001) induced the formation of GGT+ foci in the livers of initiated as well as noninitiated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Researchers isolated fumonisin B1 and B2 from Fusarium moniliforme cultures. Fumonisin B1 promoted liver cancer in rats, highlighting its toxicological significance.
Area of Science:
- Mycotoxicology
- Natural Product Chemistry
- Toxicology
Background:
- Fusarium moniliforme MRC 826 corn cultures cause leukoencephalomalacia in horses and are toxic and hepatocarcinogenic in rats.
- This isolate exhibits cancer-promoting activity, evidenced by gamma-glutamyl-transpeptidase-positive (GGT+) foci induction in rats.
Purpose of the Study:
- To isolate and identify cancer-promoting compounds from Fusarium moniliforme MRC 826 cultures.
- To utilize a cancer initiation-promotion bioassay for monitoring compound isolation.
Main Methods:
- Extraction of culture material using ethyl acetate and methanol-water.
- Chromatographic purification using Amberlite XAD-2, silica gel, and C18 reverse-phase columns.
- Bioassay monitoring for cancer-promoting activity (GGT+ foci induction).
Main Results:
- Two pure compounds, fumonisin B1 and B2, were isolated.
- Fumonisin B1 was identified as the major compound, with over 2g purified from 1kg of culture.
- Fumonisin B1 significantly induced GGT+ foci in rat livers at a 0.1% dietary level.
Conclusions:
- Fumonisin B1 and B2 are the cancer-promoting compounds isolated from Fusarium moniliforme.
- Fumonisin B1 demonstrates significant hepatocarcinogenic potential in rats, confirming its role in liver cancer promotion.