Suppressive effect of tetraprenylacetone on gastric atrophy induced by short-term administration of N-methyl-N'-nitro-N-nitrosoguanidine in rats.
BACKGROUND
Several studies have been reported on the effects of various therapeutic agents in enhancing or suppressing the carcinogenic activity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). However, it is still unknown whether a mucosal protective agent could suppress its carcinogenic activity.


METHODS
Twenty-five Wistar male rats were divided into four groups: group 1, MNNG alone; group 2, MNNG + tetraprenylacetone; group 3, control; group 4, tetraprenlacetone alone. MNNG 100 mg/mL, was freely given to groups 1 and 2, and tetraprenylacetone (200 mg/kg intraperitoneal) was additionally administered every other day to the rats in groups 2 and 4. The animals were sacrificed at 10 weeks and the gastric mucosa examined.


RESULTS
Atrophic changes were observed in the antrum after 8 weeks of oral administration of MNNG. Furthermore, using immunohistological analysis with 5-bromo-2'-deoxyuridine (BrdU), the proliferative zone was found to be enlarged and shifted upward, although the BrdU labelling index of the proliferative zone was unaltered. Intraperitoneal administration of tetraprenylacetone every other day suppressed the MNNG-induced atrophic change and the alterations proliferative markers. Tetraprenylacetone alone did not have an effect either on morphological or proliferative markers.


CONCLUSIONS
These observations suggest that gastric mucosal defensive factors may play critical roles in suppressing atrophic change inducing carcinogenesis by an exogenic carcinogen.
Miwa
H
H
Department of Gastroenterology, Juntendo University, School of Medicine, Tokyo, Japan.
Nagahara
A
A
Wada
R
R
Hirai
S
S
Endo
K
K
Watanabe
S
S
Sato
N
N
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001284:Atrophy / Q000139:chemically induced / Q000517:prevention & control; D002273:Carcinogens; D004224:Diterpenes / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008769:Methylnitronitrosoguanidine; D051381:Rats; D017208:Rats, Wistar
D000897:Anti-Ulcer Agents; D002273:Carcinogens; D004224:Diterpenes; D008769:Methylnitronitrosoguanidine; C031049:geranylgeranylacetone