Increased spindle resistance to antimicrotubule agents in women of high risk for meiotic nondisjunction

Abstract

Spindle sensitivity of phytohemagglutinin (PHA)-stimulated lymphocytes to three antimicrotubule drugs was compared in two groups of women who differ in their predisposition to meiotic aneuploidy: young women of low-risk age (ranging from 22 to 34 years) and middle-aged women of high-risk age (ranging from 40 to 52 years). Numerical sensitivity values for the antimicrotubule drugs, colchicine, podophyllotoxin, and vinblastine were obtained for each woman by recording the percentage of fully arrested metaphases out of the total metaphase cell population, i.e., cells exhibiting short, thick, and condensed chromosomes with sister chromatids clearly separated at their distal parts. Sensitivity increased linearly with increasing drug concentrations and was highly correlated with youth: its rate was significantly higher for women of the low-risk group. In addition, dividing lymphocytes of young mothers (26-33 years old) of Down syndrome children revealed significantly lower sensitivity to colchicine and podophyllotoxin than those of all young women of the low-risk group and similar sensitivity to that of the middle-aged women, i.e., the high-risk age group. The data are consistent with the theory that factors involved in meiotic nondisjunction may be concurrently operating in somatic cells. These factors presumably shift the equilibrium between tubulin and microtubules towards microtubules stabilization and thereby affect some of their functions.