Lack of effect of indomethacin on the growth of N-nitrosomethylurea-induced rat mammary tumors.

Elevated prostaglandin levels have been previously reported in mammary tumors. This study was designed to determine if treatment with indomethacin, a prostaglandin synthesis inhibitor, influenced the growth of N-nitrosomethylurea-induced mammary tumors in Wistar rats. Indomethacin was given in drinking water to tumor-bearing rats, and rats consumed between 2.5 and 3.0 mg/kg body weight/day. Continuous p.o. administration of indomethacin during 4 weeks did not affect the rate of tumor growth as compared to the control group of untreated rats. It can be concluded that indomethacin lack of effect on N-nitrosomethylurea-induced mammary tumors, and this may be due to a specific prostaglandin profile as compared with previous results using other experimental models.

Effect of prospidine administered at different times of the day on the development and growth of N-nitrosomethylurea-induced mammary tumors in Wistar rats.

The chemotherapeutic effectiveness of intraperitoneal administration of prospidine (50 mg/kg per day during the initial 14 days of study) was evaluated, on a circadian basis, on the N-nitrosomethylurea (NMU)-induced mammary tumors in female rats. Untreated rats showed a progressive increase in the mean tumor area and total tumor area/rat. At the end of treatment the average tumor area and total tumor area/rat in the animals treated at 0800, 1400 and 2000 h were significantly lower than the values in the control group by week 2. By weeks 3 and 4 the mean tumor area and total tumor area in all groups of treated rats were significantly lower than those in the untreated animals. The mean tumor area by weeks 5 and 6 in the animals treated at 0800 h were significantly lower than in the group treated at 0200 h, and the mean value by week 6 in the group treated at 1400 h was significantly lower than those from the groups treated either at 2000 h or 0200 h. The mean total tumor area/rat in rats treated at 1400 h was, by week 6, significantly lower than in animals treated either at 2000 h or 0200 h. A transient reduction in body weight was registered at the end of prospidine treatment.

[Chronotherapy of breast cancer induced by N-nitrosomethylurea in the rat. I. Effect of a high dose of cyclophosphamide administered at 8:00 and 14:00 hours]. / Cronoterapia del cáncer de mama inducido con N-nitrosometilurea en la rata. I. Efecto de una dosis elevada de ciclofosfamida administrada a las 8.00 y 14.00 horas.

The administration of cyclophosphamide (200 mg/kg) intraperitoneally produces a high mortality in Wistar rats bearing mammary tumors induced by N-methylnitrosourea. The effect is more marked when the drug is administered at 8:00 A.M. than when given at 2:00 P.M. The injection of cyclophosphamide at 2:00 P.M. slowers the tumor growth, the effect being significative after two weeks compared with the control animals, and after four weeks when compared with the animals receiving the drug at 8:00 A.M.

Chronochemotherapy of N-nitrosomethylurea-induced mammary tumors in rats. II. Circadian treatment with cyclophosphamide.

The chemotherapeutic effectiveness of intraperitoneal administration of cyclophosphamide (CY) (100 mg/kg) was evaluated, on a circadian basis, on the N-nitrosomethylurea (NMU)-induced mammary tumors in female Wistar rats. Untreated rats showed a progressive increase in the mean tumor number/rat, tumor area and total tumor area/rat. The average number of tumors/rat was significantly lower in the rats treated with CY at 02:00 h than the values obtained in the control group days 21 and 28, and than that observed at the end of the 4-week period of study in the rats treated with CY at 20:00 h. Average tumor area and total tumor area/rat in all groups of treated rats were lower than those in the untreated animals, though without significant differences amongst those treated with CY. The body weight remained constant throughout the 4-week period of study in the control group, while a transient reduction was registered after CY administration.

[Treatment with intratumoral prospidium chloride of cancer of the mammae induced by N-nitrosomethylurea in the rat]. / Tratamiento con cloruro de prospidio intratumoral del cancer de mama inducido con N-nitrosometilurea en la rata.

Wistar rats bearing N-nitrosomethylurea-induced mammary tumors received intratumoral injections of prospidium chloride or saline. Each tumor with 30-100 mm2 (the product of the two largest perpendicular diameters) received 20 mg of prospidium chloride diluted in 100 microliter of saline, and increasing amounts of 20 mg of the product in the same volume for every additional 100 mm2 or fraction of tumor. After a week the treatment was repeated in the same way. Control rats received only saline without prospidium chloride. No significant differences were observed regarding the tumor area, total tumor area/rat, and body weight when comparing the rats receiving prospidium chloride and the control rats. Prospidium chloride does not show any direct oncolytic effect upon the experimental model employed.

Human pituitary chronoendocrinology: repetitive stimulation with LRH/TRH at different times of the day.

To determine whether human pituitary is characterized by a circadian periodicity in response to repetitive injection of hypothalamic hormones, 8 healthy subjects were challenged iv with a triple stimulation with 50 micrograms of LRH and 100 micrograms of TRH in a single bolus at 0, 90 and 180 min, receiving the first pulse of hypothalamic hormones either at 02.00 h (02.00 h test) or at 09.00 h (09.00 h test). In addition, a placebo was injected instead of LRH/TRH to evaluate the spontaneous hormonal changes during the 02.00 h test. The LH, FSH, Prl and TSH basal levels were similar in the two phases studied. The mean LH, FSH and TSH peaks after each injection of LRH/TRH were similar among them. The mean Prl peak responses to the third pulse of LRH/TRH, in both the 02.00 h and the 09.00 h tests, were lower (P less than 0.05) than those after the first pulse of LRH/TRH. Placebo did not significantly change circulating LH, FSH, Prl or TSH during nocturnal sampling. The mean LH, FSH and Prl levels after LRH/TRH during the 02.00 h test were similar to those during the 09.00 h test. The mean TSH levels 15 min after the second and third pulses of LRH/TRH during the 02.00 h test were higher (P less than 0.05) than those of the 09.00 h test. Thus, thyrotropes responsiveness to pulsatile stimulation with LRH/TRH is greater during the night than in the morning, while LH, FSH and Prl responses remain constant at the two phases studied.