Chemopreventive role of Avemar in decreasing the cytotoxic effect of xenobiotics

Kocsis Z, Marcsek Z, Tompa A (2003): Chemopreventive role of Avemar in decreasing the cytotoxic effect of xenobiotics. Journal of the International Society for Advanced Cytometry.
Abstract

The chemopreventive effect of AVEMAR, a new natural medicinal product dominantly composed of substituted benzochinon (2,6-dimethoxy-p-benzochinon), extracted from fermented wheat germ was studied. Earlier studies demonstrated that AVEMAR exhibits anti-metastatic, immunrestitutive, antioxidant properties, and able to increase apoptosis. The in vitro cytotoxic effect of AVEMAR was determined using the MTT assay on both normal (MRC-5) and transformed (Vero, HepG2, MCF-7, MDA-MB-231) cell lines. MCF-7 and HepG2 cell lines are estrogen receptor positive (ER+), MDA-MB-231 does not express the estrogen receptor (ER-). Studies were performed how AVEMAR influences the cytotoxic effect of xenobiotic herbicides Atrazine, Alachlor, and Acetochlor. Atrazine (2-chloro-4-ethylamino-6-isopropylamino-3-triazine) is one of the most widely applied herbicide in the agriculture. Its stability is high therefore its persistence in the environment is long. It can be detected in the groundwater as well as in drinking water so there is a high chance of human exposition. Atrazine is known as a hormone disrupter. Genotoxicology testing of Atrazine resulted negatively but further investigation of its biological activity is necessary. On the basis of earlier data the toxic biological effect of Atrazine is developed through the disassembling of the mitochondrial electron transport system. Atrazine—and other triazines—raise the plasma progesterone levels through dopaminerg pathway so they may contribute to the initiation/development of mammary tumors. The oncogenic impact of Acetochlor is realized through non-genotoxic pathways. Formaldehyde released during the O-demethylation of Acetochlor and Alachor is supposed to contribute to the enhanced nasal tumor incidence induced by chloracetanilides. In our experiments AVEMAR was found to exhibit estrogen-like stimulatory activity in ER+ cells whereas no effect was detected on ER- cell lines. AVEMAR was found to decrease the cytotoxicity Atrazine applied in high doses on normal, non-transformed cell line. The proliferation stimulation caused by AVEMAR treatment was not influenced by low doses of Atrazine. Our results support the hypothesis that the hormone disrupter activity of Atrazine is developed through an estrogen receptor-independent pathway. In the background of Atrazine-induced increase of mammary carcinoma incidence also seems to be independent of the estrogen receptor pathways but rather due to the increase of plasma prolactin levels. The xenoestrogenic Alachlor and Acetochlor were found to produce significant proliferation enhancement of ER+ cell line and this effect was not modified considerably by AVEMAR. The proliferative effect of the xenoestrogens tested was prevented by AVEMAR on the ER- cell line Vero.

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