The effect of
ethanol (EtOH) on esophageal cell proliferation and the development of
esophageal cancers induced by
N-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 treatment 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. EtOH per se was not carcinogenic; no
tumors were seen in shrews not administered
MNNG.