Low dose induction of micronuclei by lindane

Area of Science:

• Environmental toxicology
• Molecular carcinogenesis
• Cell biology

Background:

• Environmental contaminants with hormonal activity are suspected cancer-causing agents.
• The mechanisms, genotoxic or epigenetic, underlying contaminant-induced cancer remain unclear.
• gamma-Hexachlorocyclohexane (lindane) is an environmental contaminant with hormonal activity.

Purpose of the Study:

• To investigate the genotoxic and epigenetic effects of lindane on breast (MCF-7) and prostate (PC-3) cancer cells.
• To assess lindane's impact on chromosomal damage, cell viability, cell cycle, and gene expression at environmentally relevant concentrations.

Main Methods:

• Treatment of MCF-7 and PC-3 cells with lindane across a concentration range (10(-12)-10(-4) M).
• Assessment of chromosomal damage using the cytokinesis block micronucleus assay.
• Analysis of cell viability, cell cycle kinetics, and immunocytochemical/gene expression of CDKN1A (P21WAF1/CIP1), BCL-2, and BAX.

Main Results:

• Low-dose lindane (10(-12)-10(-10) M) significantly increased micronuclei formation in both cell lines without causing cytotoxicity or DNA breaks.
• Lindane elevated Bcl-2 expression in MCF-7 cells and Bax expression in PC-3 cells at low doses.
• High-dose lindane (10(-4) M) disrupted cell cycle kinetics and altered P21WAF1/CIP1 expression differently in each cell line.

Conclusions:

• Environmental concentrations of lindane can induce chromosomal damage and alter gene expression in breast and prostate cells.
• These effects occur in the absence of cytotoxicity, suggesting epigenetic mechanisms may contribute to lindane's role in cancer.
• Lindane demonstrates greater genotoxic potential than its alpha or beta stereoisomers at the tested concentrations.