High level glucose increases mutagenesis in human lymphoblastoid cells.

Area of Science:

• Molecular Biology
• Genetics
• Cancer Research

Background:

• Epidemiological studies indicate higher cancer rates in diabetic patients.
• The mechanisms linking diabetes and cancer remain largely unknown.
• Hyperglycemia is a hallmark of diabetes mellitus.

Purpose of the Study:

• To investigate if high glucose (HG) levels are mutagenic.
• To explore the role of p53 in HG-induced mutagenesis.
• To assess the impact of antioxidant treatment on HG-induced mutations.

Main Methods:

• Mutagenesis assays were performed at hypoxanthine phosphoribosyltransferase (hprt) and thymidine kinase (tk) loci.
• Human lymphoblastoid cell lines with varying p53 statuses (wild-type, null, mutant) were used.
• Cells were treated with high glucose and/or N-acetyl-L-cysteine (an antioxidant).

Main Results:

• HG treatment significantly increased mutation fractions at both hprt and tk loci in all cell lines.
• An increase in tk mutants with normal growth rates contributed to the overall mutation increase.
• Cell lines with altered p53 (null or mutant) exhibited an earlier onset of mutagenesis compared to wild-type cells.
• N-acetyl-L-cysteine partially mitigated HG-induced mutagenesis.

Conclusions:

• High glucose is capable of inducing gene mutations.
• This mutagenic effect of hyperglycemia may contribute to cancer development in diabetic patients.
• p53 status influences the timing of mutagenesis under high glucose conditions.