To study the mechanisms of carcinogenesis, we have developed a system that uses normal cells from an environmentally and epidemiologically relevant tissue, respiratory epithelium. The induction of preneoplastic variants of epithelial cells in culture was quantitated on a per-cell basis following exposure of rat tracheal epithelial (RTE) cells in vitro to the direct-acting carcinogen N-methyl-N'...

Postconfluent cultures of Syrian hamster embryo cell strains were exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or to combinations of MNNG, hydroxyurea (HU), caffeine (CF), and/or theophylline. At various intervals, [3H]thymidine incorporation into DNA was determined by autoradiography and liquid scintillation spectrometry. In parallel cultures, drug- and/or carcinogen-elicited cytotox...

OBJECTIVE In this study, anticancer effects of mirtazapine on rats were investigated in an adenocarcinoma model induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and compared with those of cisplatin. MATERIALS AND METHODS For this purpose, 10 mg/kg doses of mirtazapine were administered orally to one group of rats, while 1 mg/kg doses of cisplatin were administered intraperitoneally to an...

The SN 1 alkylating agents activate the mismatch repair system leading to delayed G2 /M cell cycle arrest and DNA repair with subsequent survival or cell death. STAT1, an anti-proliferative and pro-apoptotic transcription factor is known to potentiate p53 and to affect DNA-damage cellular response. We studied whether STAT1 may modulate cell fate following activation of the mismatch repair syste...

DNA methylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) are potent carcinogens; their carcinogenic effect is mainly due to the effect of production of O6-methylguanine (O6 MeG) on DNA. O6 MeG is not only mutagenic but also toxic to the cell because Mer-/Mex- cells unable to remove O6 MeG are very sensitive to killing by MNNG. It has been proposed that repeated futile mismatch...

The effect of ubenimex on the progression of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced stomach tumor in rats was studied. Tumor induction was performed by giving MNNG via drinking water for 34 weeks. Ubenimex was ip administered twice a week at 0.5 mg/kg for 84 weeks in one group and 49 weeks in another starting from the first and 36th weeks after initiation of MNNG administration, re...

In the present experiment the influence of atrophic mucosa and resulting endogenous hypergastrinemia on the induction of gastric cancer by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was examined in male Donryu rats. All rats were fed MNNG in tap water for 6 months and were killed after more 5 months. The incidence of gastric cancer was 55% in rats with atrophic gastritis and hypergastrinemia, ...

The alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) is known to trigger the adaptive response by inducing the ada-regulon - consisting of three DNA repair enzymes Ada, AlkB, AlkA and the enigmatic AidB. We have applied custom designed tiling arrays to study transcriptional changes in Escherichia coli following a MNNG challenge. Along with the expected upregulation of the adaptive r...

Poly(ADP-ribosyl)ation of nuclear proteins is an immediate response of most eukaryotic cells to DNA strand breaks, as induced by carcinogen treatment. DNA amplification, on the other hand, can be induced in cell culture systems by chemical or physical carcinogens, too, reaching peak levels a few days after induction treatment. We have previously shown that 3-aminobenzamide, an inhibitor of poly...

Endoscopy can be used for sequential observation of gastric carcinogenesis in animal models. In the present study, we applied endoscopic examination and biopsy technique on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced stomach cancer in rats using a newly-developed flexible 2.5 mm endoscope. A total of 36 rats were divided into MNNG-treated and non-treated groups, observed on gastric endo...