Promoting effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone on rat glandular stomach carcinogenesis initiated with N-methyl-N'-nitro-N-nitrosoguanidine.
The modifying effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a mutagenic by-product in chlorinated water, on the development of glandular stomach cancers were investigated in Wistar rats. A total of 120 males, 6 weeks of age, were divided into six groups. After initiation with 100 ppm N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) solution and 5% NaCl diet for 8 weeks, 30 rats each in groups 1-3 were given MX in the drinking water at concentrations of 30, 10, or 0 ppm for the following 57 weeks. Ten animals each in groups 4-6 were administered the MX without prior carcinogen exposure. There were no statistical significant differences in final body weights between the groups. The incidences and multiplicities of adenocarcinomas in the glandular stomachs were significantly higher (P < 0.05) in the initiated 30 ppm MX group than those in the MNNG/NaCl group. The incidences of atypical hyperplasias in the glandular stomachs were also significantly increased (P < 0.05 or 0.01) by the MX treatments. With their multiplicity, the effects were clearly dose dependent. Interestingly, the 30 ppm MX alone itself induced atypical hyperplasias in the pylorus, although the incidences and severity were low. Moreover, MX showed a tendency to enhance the development of intrahepatic cholangiocellular tumors and thyroid follicular cell tumors in the MNNG-treated animals. The results of the present study thus indicate that MX exerts promoting effects when given during the postinitiation phase of two-stage glandular stomach carcinogenesis in rats.
Nishikawa
A
A
Division of Pathology, National Institute of Health Sciences, Tokyo, Japan. nishikaw@nihs.go.jp
Furukawa
F
F
Lee
I S
IS
Kasahara
K
K
Tanakamaru
Z
Z
Nakamura
H
H
Miyauchi
M
M
Kinae
N
N
Hirose
M
M
D000230:Adenocarcinoma / Q000139:chemically induced*; D018263:Adenocarcinoma, Follicular / Q000139:chemically induced; D002759:Adenoma, Bile Duct / Q000139:chemically induced; D000818:Animals; D001650:Bile Duct Neoplasms / Q000139:chemically induced; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D018281:Cholangiocarcinoma / Q000139:chemically induced; D003043:Cocarcinogenesis; D005355:Fibrosis; D005663:Furans / Q000633:toxicity*; D006965:Hyperplasia; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology; D011708:Pylorus / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013272:Stomach Diseases / Q000139:chemically induced / Q000473:pathology; D013274:Stomach Neoplasms / Q000139:chemically induced*; D013964:Thyroid Neoplasms / Q000139:chemically induced; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D002273:Carcinogens; D005663:Furans; D009153:Mutagens; D014874:Water Pollutants, Chemical; D008769:Methylnitronitrosoguanidine; C054121:3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone