methylnitronitrosoguanidine and Weight-Gain

Sulpiride and ethylene glycol monomethyl ether (EGME) are known ovarian toxicants that stimulate prolactin (PRL) secretion, resulting in hypertrophy of the corpora lutea and increased progesterone (P4) production. The purpose of the present study was to investigate how the PRL stimulatory agents affected uterine carcinogenesis and to clarify the effects of PRL on endometrial adenocarcinoma progression in rats. Ten-week-old female Donryu rats were treated once with N-ethyl-N'-nitro-N-nitrosoguanidine (20 mg kg(-1) ), followed by treatment with sulpiride (200 ppm) or EGME (1250 ppm) from 11 weeks of age to 12 months of age. Sulpiride treatment inhibited the incidence of uterine adenocarcinoma and precancerous lesions of atypical endometrial hyperplasia, whereas EGME had no effect on uterine carcinogenesis. Sulpiride markedly prevented the onset of persistent estrus throughout the study period, and EGME delayed and inhibited the onset of persistent estrus. Moreover, sulpiride-treated animals showed high PRL and P4 serum levels without changes in the levels of estradiol-17β, low uterine weights and histological luteal cell hypertrophy. EGME did not affect serum PRL and P4 levels. These results suggest that the prolonged low estradiol-17β to P4 ratio accompanied by persistent estrous cycle abnormalities secondary to the luteal stimulatory effects of PRL may explain the inhibitory effects of sulpiride on uterine carcinogenesis in rats. Copyright © 2015 John Wiley & Sons, Ltd.

Topics: Adenocarcinoma; Animals; Anticarcinogenic Agents; Carcinogenesis; Carcinogens; Endometrial Hyperplasia; Endometrial Neoplasms; Endometrium; Estrus; Ethylene Glycols; Female; Infertility, Female; Methylnitronitrosoguanidine; Organ Size; Ovary; Precancerous Conditions; Progesterone; Prolactin; Rats, Inbred Strains; Sulpiride; Uterus; Weight Gain

Short-term assays in vivo have suggested that hickory smoke condensate (HSC), a food flavouring, might have tumour-initiating and/or promoting activities in the glandular stomach of the rat. In the present study, the modifying effects of HSC on glandular stomach carcinogenesis after initiation with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and sodium chloride (MNNG salt) were investigated in male Wistar rats. Animals were given MNNG solution (100 ppm) as drinking water and simultaneously fed the diet supplemented with 5% sodium chloride for 8 wk. Matched negative controls received neither MNNG nor sodium chloride. Rats were then fed a basal diet and given HSC solution (1 or 3%) or tap water for the following 32 wk. During the experimental period, treatment with MNNG salt and administration of HSC both brought about growth retardation although the final body weight of rats was comparable between groups. Only two rats treated with MNNG salt followed by 1% HSC developed adenocarcinoma of the stomach. HSC treatment appeared to increase the number of rats with preneoplastic hyperplasias and/or adenocarcinomas in both the fundic and pyloric mucosa, although not to a statistically significant extent. HSC administration significantly increased malondialdehyde levels in the urine and gastric mucosa, the former in a dose-dependent manner. The results suggest that HSC has little, if any, promoting effect on two-stage glandular stomach carcinogenesis in rats when given during the post-initiation phase. However, the tumour co-initiating effects of HSC require further clarification.

Topics: Adenocarcinoma; Animals; Diet; Drinking; Flavoring Agents; Gastric Mucosa; Hyperplasia; Male; Malondialdehyde; Methylnitronitrosoguanidine; Precancerous Conditions; Rats; Rats, Wistar; Smoke; Sodium Chloride; Stomach Neoplasms; Weight Gain; Wood