Induction and persistence of micronuclei, sister-chromatid exchanges and chromosomal aberrations in splenocytes and bone-marrow cells of rats exposed to ethylene oxide.
Studies on the induction and persistence of ethylene oxide (EO) induced chromosomal alterations in rat bone-marrow cells and splenocytes following in vivo exposure were carried out. Rats were exposed to ethylene oxide either chronically by inhalation (50-200ppm, 4 weeks, 5 days/week, 6h/day) or acutely by intraperitoneal injection (i.p.) at dose levels of 50-100ppm.Spontaneous- and induced-frequencies of micronuclei (MN), sister-chromatid exchanges (SCEs) and chromosomal aberrations were determined in rat bone-marrow cells, and in splenocytes following in vitro mitogen stimulation. Unstable chromosomal aberrations were studied in whole genome using standard Giemsa staining technique and fluorescence in situ hybridisation using probe for chromosome #2 was employed to detect chromosome translocations. Following chronic exposure, the cytogenetic analyses were carried out at days 5 and 21 in rat splenocytes, to study the induction and persistence of sister-chromatid exchanges. Following chronic exposure, ethylene oxide was effective in inducing SCEs, and markedly cells with high frequency SCEs were observed and they in-part persisted until day 21 post-exposure. However, no significant effect was observed in rat splenocytes for induction of MN and chromosomal aberrations. Following acute exposure, both SCEs and MN were increased significantly in rat bone-marrow cells as well as splenocytes.In conclusion, this study indicates that ethylene oxide at the concentrations employed by intraperitoneal injection or inhalation in adult rats is mutagenic and can induce both SCEs and MN.
Lorenti Garcia
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MGC, Department of Radiation Genetics and Chemical Mutagenesis, Leiden University Medical Centre, Wassenaarseweg 72, 2333 AL, Leiden, The Netherlands.
Darroudi
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F
Tates
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AD
Natarajan
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AT
D000280:Administration, Inhalation; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D002869:Chromosome Aberrations; D004305:Dose-Response Relationship, Drug; D005027:Ethylene Oxide / Q000008:administration & dosage / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D008297:Male; D015162:Micronucleus Tests; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011917:Rats, Inbred Lew; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013154:Spleen / Q000166:cytology / Q000187:drug effects*
D009153:Mutagens; D005027:Ethylene Oxide