Mutations in immunoglobulin-producing mouse myeloma cells.

Area of Science:

• * Molecular biology
• * Cell biology
• * Genetics

Background:

• * Myeloma cells are used to study protein secretion.
• * Understanding protein synthesis defects is crucial for disease research.

Purpose of the Study:

• * To identify and characterize variants of mouse myeloma cells defective in myeloma protein secretion.
• * To investigate the spontaneous mutation rate of protein secretion defects.
• * To examine the effect of a chemical mutagen on the frequency and nature of these variants.

Main Methods:

• * Cloning of mouse myeloma cell lines in soft agar.
• * Antiserum overlay method for screening protein secretion variants.
• * Treatment with the acridine half mustard ICR-191 to induce mutations.

Main Results:

• * High spontaneous rate (10^-3) of variants losing heavy chain synthesis.
• * Concomitant loss of light chain production in these variants.
• * Increased variant incidence and altered heavy chain synthesis after ICR-191 treatment.

Conclusions:

• * Myeloma protein heavy and light chain synthesis are coordinately regulated.
• * Genetic instability contributes to high rates of secretion defects in myeloma cells.
• * Chemical mutagens can induce novel protein variants.