Effect of ethanol on esophageal cell proliferation and the development ofN-methyl-N′-nitro-N-nitrosoguanidine induced-esophageal carcinoma in shrews

Abstract

The effect of ethanol (EtOH) on esophageal cell proliferation and the development of esophageal cancers induced byN-methyl-N′-nitro-N-nitrosoguanidine (MNNG) in shrews were investigated. Sequential histological examination was done, and cell proliferation was assessed by BrdU labeling. At 5 weeks of age, animals were given tap water, 2% EtOH, 50 ppm MNNG, or 50 ppm MNNG plus 2%, 5% or 10% EtOH in the drinking water. Administration of 10% and 5% EtOH simultaneously with MNNG caused death in 40% (10/25) within 4 days and in 20% (6/30) within 7 days respectively, whereas other treatments were well tolerated with no sudden deaths. Administration of 2% EtOH for 30 weeks caused a 2-fold increase, and that of MNNG caused a 4.5-fold increase in the proliferation index of the basal cells of the esophagus compared with control shrews, and MNNG plus 2% EtOH caused a 5.5-fold increase. In MNNG-treated shrews, with or without 2% EtOH administration, sequential histological examination of esophageal tissue revealed a similar change; dysplasia appeared at 30 weeks of age, squamous cell carcinoma occurred at 35 weeks of age, and the depth of invasion extended to adventitia at 45 weeks of age. These finding indicate that treatment with 2% EtOH promoted the proliferation of esophageal basal cells but did not alter the tumor induction period and did not have tumor-promoting activity. EtOHper se was not carcinogenic; no tumors were seen in shrews not administered MNNG.

Abbreviations

MNNG

N-methyl-N′-nitro-N-nitrosoguanidine

BrdU

5-bromo-2′-deoxyuridine

PI pro

liferating index