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Effect of Gastrin on Gastric Mucosal Cyclic Adenosine 3':5'-Monophosphate-dependent Protein Kinase Activity in Rat Stomach Carcinogenesis Induced by N-Methyl-N'-nitro-N-nitrosoguanidine¹

First Department of Pathology, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minemi-ku, Hiroshima 734, Japan

This was a study of the effects of gastrin on gastric mucosal cyclic-adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase activity and DNA synthesis in rat stomach carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in order to clarify the mechanism of the enhanced effect of gastrin on the early stage of stomach carcinogenesis. Inbred Basel-Wistar rats received MNNG in drinking water (50 µg/ml for 32 weeks) and were treated with s.c. injections of pentagastrin (300 µg/kg twice daily for 4 weeks) beginning with the fourth and eighth weeks after the initiation of MNNG treatment. The incidence of gastric adenocarcinoma in fourth-week gastrin-treated rats and of gastric carcinoid in eighth-week gastrin-treated rats was higher than that in rats treated with MNNG alone. The former tumors developed in the antrum and most of the latter tumors in the fundus. In the early stage of carcinogenesis the labeling index ([³H]thymidine-labeled nuclei/one gland) in both the antrum and fundus was the same in MNNG-plus-gastrin-treated groups and in the MNNG-only-treated group. With regard to the distribution of cAMP-dependent protein kinase isoenzyme in fourth-week gastrin-treated rats, the proportion of type I cAMP-dependent protein kinase significantly increased in the antrum during the eighth week after the initiation of MNNG treatment (P < 0.01). The increased type I activity in the antrum of the gastrin-treated rats agreed with the high incidence of gastric adenocarcinoma in the antrum. Type I isoenzyme clearly increased in gastric adenocarcinoma. These results suggest that type I cAMP-dependent protein kinase can play an important role in the enhanced effect of gastrin on rat stomach carcinogenesis induced by MNNG.

¹ Supported in part by Grants-in-Aid for Cancer Research from the Ministry of Education, Science and Culture of Japan (58010070, 59010074).

² To whom requests for reprints should be addressed.

Received 1/22/85. Revised 5/ 9/85. Accepted 6/20/85.

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