The apparent decrease in thiotepa-induced chromosome aberrations in human lymphocytes caused by an effect of WR2721...

Area of Science:

• Cell Biology
• Genetics
• Radioprotection

Background:

• Antimutagenic radioprotective compounds can decrease chemically induced chromosome aberrations.
• The mechanism for this observed decrease, especially when administered before the mutagen thio-TEPA, is unclear.
• It was hypothesized that the protective compound might alter cell cycle progression, affecting aberration scoring.

Purpose of the Study:

• To investigate whether antimutagens affect cell cycle progression, leading to an artifactual decrease in thio-TEPA-induced chromosome aberrations.
• To determine if the protective compound WR2721 influences the timing of cell division after thio-TEPA treatment.

Main Methods:

• Human lymphocytes were treated with WR2721 followed by thio-TEPA.
• Cells were cultured with 5-bromodeoxyuridine (BrdU) to distinguish cells based on the number of divisions after treatment.
• Chromosome aberration yields were analyzed in first, second, and subsequent division cells.

Main Results:

• The yield of aberrations in first-division cells was unaffected by the presence of WR2721.
• A reduction in aberration yields was observed only in rapidly cycling cells in their second division.
• Labeling experiments indicated that fewer of these rapidly cycling cells were in the G2 phase when thio-TEPA was administered.

Conclusions:

• The observed decrease in chromosome aberration yields by antimutagens administered hours before a mutagen is partly an artifact of cell selection.
• WR2721 does not directly reduce thio-TEPA-induced aberrations in all cells but influences the cell cycle distribution of scored cells.