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Influence of mancozeb on mitogenically responsive lipids in rat cerebrum and liver
A Subramoniam1, D Agrawal, S P Srivastava
1Industrial Toxicology Research Centre, Lucknow, India.
Abstract:
Mancozeb, a commonly used fungicide, has been shown to induce tumours in mouse skin and maneb, unit constituent of mancozeb, is reported to induce tumours in rats. The mechanism by which mancozeb induced tumorigenicity is not known. Since the levels of inositol phospholipids and phosphatidic acid have roles in the regulation of cell proliferation, the effects of mancozeb on the levels of these lipids were studied in rats. Daily oral administration of commercial grade mancozeb at a concentration of 50 mg/kg body wt for 30 days (5 days a week) caused no significant change in the levels of inositol phospholipids and phosphatidic acid (PA) in both cerebrum and liver, while at high concentration (250 mg/kg body wt) under the same treatment schedule mancozeb increased the levels of these lipids. In cerebrum, the levels of phosphatidylinositol (PI) and PA were increased by 36 and 43% respectively without affecting the levels of polyphosphoinositides, whereas in liver the levels of not only PI (50%) and PA (49%) but also those of polyphosphoinositides were increased. These results show that mancozeb influences the levels of PA and inositol phospholipids, involved in phospholipase C-pathway of signalling.
Insights
Mancozeb, a fungicide, may cause tumors by altering cell signaling lipids. High doses significantly increased phosphatidic acid (PA) and inositol phospholipids in rat brains and livers, suggesting a potential mechanism for tumorigenicity.
Area of Science:
- Toxicology
- Biochemistry
- Cell Biology
Background:
- Mancozeb is a widely used fungicide with known tumorigenic effects in animal models.
- The precise mechanism underlying mancozeb-induced tumorigenicity remains unclear.
- Inositol phospholipids and phosphatidic acid are critical regulators of cell proliferation.
Purpose of the Study:
- To investigate the impact of mancozeb exposure on the levels of inositol phospholipids and phosphatidic acid (PA) in rats.
- To explore the potential role of these lipids in mancozeb's tumorigenic effects.
Main Methods:
- Rats were administered commercial grade mancozeb orally at doses of 50 mg/kg or 250 mg/kg body weight, 5 days a week for 30 days.
- Levels of inositol phospholipids and phosphatidic acid were quantified in cerebrum and liver tissues.
Main Results:
- Low-dose mancozeb (50 mg/kg) did not significantly alter inositol phospholipid or PA levels in the brain or liver.
- High-dose mancozeb (250 mg/kg) significantly increased phosphatidylinositol (PI) and PA levels in the cerebrum (36% and 43%, respectively).
- In the liver, high-dose mancozeb elevated PI (50%), PA (49%), and polyphosphoinositide levels.
Conclusions:
- Mancozeb exposure, particularly at higher concentrations, influences the levels of phosphatidic acid and inositol phospholipids.
- These lipid alterations suggest that mancozeb may affect cell signaling pathways, specifically the phospholipase C pathway.
- The findings provide insights into the potential biochemical mechanisms contributing to mancozeb's tumorigenicity.