Enhancing effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) on cell proliferation and lipid peroxidation in the rat gastric mucosa.
The influence of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone, a mutagen in chlorinated water, on cell proliferation and lipid peroxidation in the glandular stomach mucosa was investigated in male 4-week-old Wistar rats. Animals were given 50 p.p.m., 25 p.p.m., 12.5 p.p.m., 6.25 p.p.m. or 0 p.p.m. of MX solution in their drinking water for 5 weeks. At the end of this period, cell proliferation in the mucosal epithelia of the gastric fundus was increased in a dose-dependent manner up to 25 p.p.m., at which dose the induction was statistically significant as compared with the control value (P < 0.05). The MX treatment was also associated with increased lipid peroxidation levels in the gastric mucosa as well as in the urine, with loose dose-dependence, although not at 50 p.p.m. Mucosal lipid peroxidation was significantly increased in animals given 25 p.p.m. as compared with controls (P < 0.05). Similarly, the levels of urinary lipid peroxidation were significantly higher in rats given 25 p.p.m. or 12.5 p.p.m. than in the controls (P < 0.05). Histopathologically, gastric erosion was noted in rats receiving 25 p.p.m. or more of MX. There were no statistical differences between groups for serum biochemical data. The results thus suggest that MX may exert a gastric tumor-promoting action in rats, even at low doses which do not give rise to toxic effects, because of the clear dose-response relationship evident at low levels.
Division of Pathology, National Institute of Health Sciences, Tokyo, Japan.
A
A
Nishikawa
N
N
Kinae
F
F
Furukawa
M
M
Mitsui
T
T
Enami
T
T
Hasegawa
M
M
Takahashi
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D004231:Diuresis / Q000187:drug effects; D005663:Furans / Q000008:administration & dosage*; D005753:Gastric Mucosa / Q000187:drug effects*; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D009153:Mutagens; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D005663:Furans; D008054:Lipid Peroxides; D009153:Mutagens; C054121:3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone