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 alike. There is, however, no clear evidence from human biomonitoring studies or animal experiments showing that in vivo exposure of resting lymphocytes to an aneuploidogen could actually be expressed as MN in cultured lymphocytes. In vitro, a pulse treatment of human lymphocytes with vinblastine, an aneuploidogen, did result in MN induction even if performed before mitogen stimulation, although a much more pronounced effect was obtained in actively dividing lymphocyte cultures. On the other 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 second cell cycle interphase cells in the MN assay, is able to slightly increase the level of MN with whole chromosomes. If MN harboring chromosome 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 difficulty 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.
Norppa
H
H
Department of Industrial Hygiene and Toxicology, Institute of Occupational Health, Helsinki, Finland.
Luomahaara
S
S
Heikanen
H
H
Roth
S
S
Sorsa
M
M
Renzi
L
L
Lindholm
C
C
D000782:Aneuploidy; D001483:Base Sequence; D002478:Cells, Cultured; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000648:ultrastructure; D015162:Micronucleus Tests; D008969:Molecular Sequence Data; D008991:Monitoring, Physiologic; D009153:Mutagens / Q000633:toxicity*; D012680:Sensitivity and Specificity
D009153:Mutagens