Induction of kinetochore-positive micronuclei in human lymphocytes by the anti-fungal drug griseofulvin.
Griseofulvin (GF) is a widely used antifungal drug for the treatment of superficial dermatomycoses. However, because GF is carcinogenic and teratogenic in animal models there is considerable concern regarding its clinical application. Further, it produces numerical chromosome aberrations in human lymphocytes and cell lines. There are conflicting reports on the ability of GF to induce structural chromosomal aberrations. Here, we show GF induces micronucleus formation both in isolated peripheral lymphocytes and lymphocytes from whole blood cultures. An antikinetochore antibody was used to distinguish micronuclei with acentric chromosome fragments (kinetochore-negative) and from those containing whole chromosomes (kinetochore-positive). The micronuclei formed were 99% kinetochore-positive in isolated lymphocytes. In addition, GF was able to alter the cell cycle kinetics of lymphocytes, thereby increasing the percentage of triploid cells. We conclude that GF is a strong aneuploidy-inducing agent in peripheral human lymphocytes and produces effects at concentrations which should be detectable in the blood of persons undergoing therapy.
Kolachana
P
P
Center for Occupational and Environmental Health, School of Public Health, University of California, Berkeley 94720.
Smith
M T
MT
D000782:Aneuploidy; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006118:Griseofulvin / Q000633:toxicity*; D006801:Humans; D008214:Lymphocytes / Q000648:ultrastructure; D015162:Micronucleus Tests / Q000379:methods*
D006118:Griseofulvin