Comparative study on susceptibility to 1-bromopropane in three mice strains.
Previous studies indicate that 1-bromopropane (1BP) has neurotoxicity and reproductive toxicity both in humans and animals. The present study investigated strain differences in susceptibility to 1BP and identified possible biological factors that determine such susceptibility. Twenty-four male mice of each of the three strains (C57BL/6J, DBA/2J, and BALB/cA) were divided into four groups of six each and exposed to 1BP at 0, 50, 110, and 250 ppm for 8 h/day for 28 days by inhalation. At the end of exposure period, the relative susceptibilities of each strain to 1BP-mediated hepatotoxicity and male reproductive toxicity were evaluated. The contributing factors to strain-dependent susceptibility were assessed by determination of hepatic CYP2E1 levels, glutathione-S-transferase (GST) activity, glutathione (GSH) status, and NAD(P)H:quinone oxidoreductase and heme oxygenase-1 mRNA levels. Liver histopathology showed significantly larger area of liver necrosis and more degenerative lobules in BALB/cA in the order of BALB/cA > C57BL/6J > DBA/2J. BALB/cA showed higher CYP2E1 protein level and lower total GSH content and GST activity in the liver than DBA/2J. These results indicate that BALB/cA mice are the most susceptible to hepatotoxicity of 1BP among the three strains tested, and that CYP2E1, GSH level/GST activity may contribute to the susceptibility to 1BP hepatotoxicity. Exposure to > or = 50 ppm of 1BP also decreased sperm count and sperm motility and increased sperms with abnormal heads in all three strains mice in a dose-dependent manner. Comparison with previous studies in rats indicates that mice are far more susceptible than rats to 1BP regarding hepatotoxicity and reproductive toxicity.
Liu
Fang
F
Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Ichihara
Sahoko
S
Mohideen
Sahabudeen Sheik
SS
Sai
Uka
U
Kitoh
Junzoh
J
Ichihara
Gaku
G
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006842:Hydrocarbons, Brominated / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009929:Organ Size / Q000187:drug effects; D011808:Quinone Reductases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013076:Sperm Count; D013081:Sperm Motility
D017931:DNA Primers; D006842:Hydrocarbons, Brominated; D019392:Cytochrome P-450 CYP2E1; D006419:Heme Oxygenase (Decyclizing); C041831:NADH dehydrogenase (quinone); D011808:Quinone Reductases; D005982:Glutathione Transferase; D005978:Glutathione; C118559:1-bromopropane