A comparative study of gene expression profiles in rat liver after administration of alpha-hexachlorocyclohexane and lindane.
Alpha-hexachlorocyclohexane (alpha-HCH) is a stereoisomer of gamma-HCH, the active ingredient of lindane (> 99% gamma-HCH). In the present study, cDNA microarray technology was employed to identify changes in gene expression associated with toxicity in livers of male Fischer 344 rats after treatment with alpha-HCH (2, 20 mg/kg/day) and lindane (1, 10 mg/kg/day) by daily oral gavage for up to 28 days. Liver samples were obtained after 1, 3, 7, 14 and 28 days and compared for gene expression profiles. The dose of the alpha-HCH was higher than that of lindane and toxicity was greater, but the numbers of probe sets with differences in expression were fewer for the alpha-HCH-treated group except on Day 3. Only very few probe sets with differences in expression overlapped between alpha-HCH and lindane at each time point and the gene expression profiles were very dissimilar. Important liver-based differences in expression between alpha-HCH and lindane might possibly account for hepato-carcinogenicity of alpha-HCH.
Sumida
Kayo
K
Sumitomo Chemical Co. Ltd., 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-8558, Japan. sumida@sc.sumimoto-chem.co.jp
Saito
Koichi
K
Oeda
Kenji
K
Yakabe
Yoshikuni
Y
Otsuka
Masanori
M
Matsumoto
Hiroshi
H
Sekijima
Masaru
M
Nakayama
Koji
K
Kawano
Yukiko
Y
Shirai
Tomoyuki
T
D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D016000:Cluster Analysis; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D001556:Hexachlorocyclohexane / Q000008:administration & dosage / Q000633:toxicity*; D007441:Intubation, Gastrointestinal; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors