Antioxidant induces DNA damage, cell death and mutagenicity in human lung and skin normal cells

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Clinical trials indicate antioxidant supplementation may elevate cancer risk.
• The molecular mechanisms behind this increased risk remain largely unknown.
• Epigallocatechin gallate (EGCG) is a prominent antioxidant studied for its biological effects.

Purpose of the Study:

• To investigate the molecular mechanism by which EGCG affects normal and cancerous cells.
• To determine if EGCG induces DNA damage and cell death in human lung and skin cells.
• To elucidate the role of reductive mechanisms in EGCG-induced cellular toxicity.

Main Methods:

• Exposure of human lung and skin normal cells to EGCG.
• Assessment of cell viability, DNA damage (double-strand breaks), apoptosis, and mutation frequency.
• Comparison of EGCG toxicity with known toxic agents like H₂O₂ and cisplatin.

Main Results:

• EGCG induced significant cell death and DNA damage in normal human lung and skin cells via a reductive mechanism.
• EGCG demonstrated higher toxicity to normal cells than H₂O₂ and cisplatin.
• Low concentrations of EGCG (≤100 μM) slightly enhanced lung cancer cell viability.
• EGCG triggered DNA double-strand breaks, apoptosis, and increased mutation frequency in normal cells.

Conclusions:

• EGCG's reductive mechanism explains its toxicity to normal cells, providing a molecular basis for clinical findings on antioxidant supplementation and cancer risk.
• This study reveals a novel reductive DNA damaging pathway.
• Findings offer new insights into aging and disease, potentially guiding prevention and therapeutic strategies.