High incidence of esophageal cancer in esophageal achalasia by the oral administration of N-amyl-N-methylnitrosamine and its prevention by nicardipine hydrochloride in mice.
Esophageal achalasia (EA) is a rare disease in man and animals and there are many discussions on its higher risk of esophageal cancer. N-Amyl-N-methylnitrosamine (AMN) which specifically induces esophageal tumors in mice and rats was given to three mutant mouse strains, i.e. 101/N, STX/Le and BXH-8, which develop a high incidence of EA. The incidence of EA in 101/N, STX/Le, BXH-8 and normal C57BL/6J mice was 38.5% (110/286), 30.1% (43/143), 91.8% (190/207) and 0% (0/167), respectively. The average numbers of AMN-induced esophageal tumors in EA(+) were significantly higher than those of EA(-) in all of the 101/N, STX/Le and BXH-8 mice. Furthermore, significantly larger size tumors and invasive squamous cell carcinomas were found in EA(+) mice than in EA(-) mice. These results indicate the higher sensitivity of EA for both tumor induction and promotion, possibly due to the longer retention of AMN. In fact, relaxation of the lower esophagus by a smooth muscle relaxing calcium-channel blocker, nicardipine hydrochloride, significantly prevented the induction of esophageal tumors.
Kurooka
M
M
Department of Radiation Biology, Faculty of Medicine, Osaka University, Suita, Japan.
Hongyo
T
T
Nakajima
H
H
Baskar
R
R
Li
L Y
LY
Fukuda
K
K
Sutoh
K
K
Miyata
M
M
Matsuda
H
H
Nomura
T
T
D000284:Administration, Oral; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced*; D004931:Esophageal Achalasia / Q000209:etiology*; D004938:Esophageal Neoplasms / Q000139:chemically induced / Q000150:complications* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009529:Nicardipine / Q000494:pharmacology*; D009602:Nitrosamines; D012306:Risk
D002121:Calcium Channel Blockers; D002273:Carcinogens; D009602:Nitrosamines; C025033:N-amyl-N-methylnitrosamine; D009529:Nicardipine