MECHANISMS OF NONDISJUNCTION AND IMPLICATIONS FOR TESTING ANEUGENS

THE HUMAN SPECIES IS AFFECTED BY A HIGH FREQUENCY OF CONSTITUTIONAL ANEUPLOIDY WHICH IS MAINLY DERIVED FROM NONDISJUNCTION DURING PARENTAL MEIOSIS AND PREFERENTIALLY DURING MATERNAL MEIOSIS I. IN UNRAVELLING THE MECHANISMS INVOLVED WE STUDIED VARIOUS CONDITIONS CAUSING AND ASSOCIATED WITH NONDISJUNCTION IN OOCYTES FROM DJUNGARIAN HAMSTERS. CONSIDERING OUR OBSERVATIONS WE SUGGEST THAT THE ORDERLY SEGREGATION OF CHROMOSOMES AT MEIOSIS APPEARS TO RESULT FROM A CASCADE OF DIFFERENTIATION PROCESSES REQUIRING THE INTERACTION OF AN EXTRA-, TRANS- AND INTRACELLULAR SIGNALLING. FAILURES MAY OCCUR AT ANY LEVEL ALTERING E.G.: (1) THE CONTROL OF FOLLICULAR MATURATION/FUNCTION (OR GENERALLY THE FUNCTION OF THE SOMATIC COMPARTMENT WITHIN THE GONADS) (2) THE SIGNALLING BETWEEN SOMA AND MEIOCYTE (3) THE FUNCTION OF THE CYTOPLASM AND CYTOPLASMIC ORGANELLES SUCH AS THE SPINDLE AND MITOCHONDRIA (BEERMANN ET AL. 1988) (3) THE RATE OF MEIOSIS (5) CHROMOSOME BEHAVIOR AND THEIR INTERACTION WITH MICROTUBULI. NONDISJUNCTION APPEARS TO BE ONE CONSEQUENCE OF A DISTURBED CONTROL OF MEIOCYTE PROLIFERATION. THE CAUSES MIGHT, IN ANALOGY, BE AS DIVERSE AS THOSE LEADING TO NEOPLASTIC GROWTH OF SOMATIC CELLS. NOTWITHSTANDING THE NECESSITY FOR SIMPLIFICATION IN MUTAGENICITY TESTING ONE HAS TO REMIND THAT THE MAJORITY OF TRISOMIES ORIGINATE FROM A MEIOSIS I ERROR. SO FAR WE CAN NOT BE SURE THAT SOMATIC CELL TESTING MAY INDICATE PUTATIVE EVENTS DURING THE ABOVE DESCRIBED COMPLICATED INTERACTIVE MATURATION PROCESS OF GERM CELLS.