Genotoxic effects of butadiene in mouse lung cells detected by an ex vivo micronucleus test.
Lung fibroblasts from BD-exposed mice have been analysed for the occurrence of micronuclei. Primary cultures set up 24h after the end of exposure were treated with cytochalasin B and micronuclei scored in binucleate cells. A three-fold statistically significant increase of micronucleated cells was detected after exposure to 500ppm, the lowest tested concentration. A linear dose effect relationship was observed between 500 and 1300ppm. Immunofluorescent staining of kinetochore proteins was applied to distinguish between acentric micronuclei produced by chromosome breaks and micronuclei containing a centromeric region, most likely induced by chromosome loss. A statistically significant increase of both types of MN in 1300ppm-exposed females and a significant increase in centromeric MN in 500ppm-exposed males were detected. These data demonstrate that an intermediate of BD metabolism with a potential for clastogenic and aneugenic effects is active in lung cells after inhalation exposure. These effects can play a role in the initiation and promotion of BD-induced lung tumours.
Ranaldi
R
R
Section of Toxicology and Biomedical Sciences, ENEA CR Casaccia, Via Anguillarese 301, 00060, Roma, Italy.
Bassani
B
B
Pacchierotti
F
F
D000818:Animals; D002070:Butadienes / Q000633:toxicity*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*
D002070:Butadienes; D009153:Mutagens