Genotoxicity of malathion in human lymphocytes assessed using the micronucleus assay in vitro and in vivo: a study of malathion-exposed workers.
The aerial application of malathion, a widely used organophosphate insecticide, has raised public concerns about potential adverse health effects. We therefore studied micronucleus formation in human lymphocytes as a biomarker of genotoxicity both in vitro and in vivo. Lymphocytes were cultured either as whole blood or after Ficoll isolation and treated with malathion in doses from 5 to 100 micrograms/ml for 48 h. A significant increase in micronucleated cells (47.5/1000 versus 16.0/1000 in DMSO control, p < 0.001) was found in isolated lymphocytes at high dose levels (75-100 micrograms/ml), concurrent with cytotoxicity and a strong inhibition of proliferation (p < 0.001). Many of the treated cells also possessed multiple micronuclei. Antikinetochore-antibody staining revealed that the majority of malathion-induced micronuclei were kinetochore-negative. A significant dose-response was also observed in whole blood cultures, although the increase in micronucleated cells was lower than in isolated lymphocyte cultures (p = 0.03). When the same technique was applied to lymphocytes of 38 intermittently malathion-exposed workers involved in the Mediterranean Fruit Fly Eradication Program in California, no change in either proliferation or micronucleus level was observed compared with an unexposed control group. We conclude that malathion has a relatively low potential to cause chromosome damage in vitro, and corresponding doses are much higher than ones that even professional applicators are likely to be exposed to in vivo. The potential risk of chromosome damage for malathion exposure in vivo is therefore relatively low. More studies are needed to assess the possibility of interaction of malathion with other pesticides through combined exposure.
Titenko-Holland
N
N
Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley 94720, USA. ninah@uclink4.berkeley.edu
Windham
G
G
Kolachana
P
P
Reinisch
F
F
Parvatham
S
S
Osorio
A M
AM
Smith
M T
MT
D000428:Alcohol Drinking; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D008294:Malathion / Q000633:toxicity*; D008297:Male; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D016273:Occupational Exposure; D012016:Reference Values; D012737:Sex Factors; D012907:Smoking; D013050:Spectrometry, Fluorescence / Q000379:methods
D009153:Mutagens; D008294:Malathion