MICRONUCLEUS ASSAY IN LYMPHOCYTES AS A TOOL TO BIOMONITOR HUMAN EXPOSURE TO ANEUPLOIDOGENS AND CLASTOGENS

The analysis of micronuclei (MN) in cultured human lymphocytes is, in principle, able to detect exposure to clastogens and aneuploidogens al ike. There is, however, no clear evidence from human biomonitoring stu dies or animal experiments showing that in vivo exposure of resting ly mphocytes to an aneuploidogen could actually be expressed as MN in cul tured lymphocytes. In vitro, a pulse treatment of human lymphocytes wi th vinblastine, an aneuploidogen, did result in MN induction even if p erformed before mitogen stimulation, although a much more pronounced e ffect was obtained in actively dividing lymphocyte cultures. On the ot her hand, it is probable that a considerable portion of ''spontaneous' ' MN contain whole chromosomes, their contribution increasing with age . It also seems that cytochalasin B, used for the identification of se cond cell cycle interphase cells in the MN assay, is able to slightly increase the level of MN with whole chromosomes. If MN harboring chrom osome fragments represent a minority of the total MN frequency, there may be difficulties in detecting a weak effect in this fraction of MN against the background of MN with whole chromosomes. This would reduce the sensitivity of the assay in detecting clastogens, unless MN with whole chromosomes and chromosome fragments are distinguished from each other. That a problem may exist in sensitivity is suggested by the di fficulty in demonstrating MN induction by smoking, an exposure capable of inducing chromosome aberrations. The sensitivity of the lymphocyte MN assay could be increased by detecting kinetochore or centromere in MN, or by automation, allowing more cells to be analyzed.