Abstract
Reserpine 50 μg 100 g body weight administered s.c. to female rats on the day before, of and after each of three N-nitrosomethylurea (NMU) i.v. injections, influenced a number of experimental observations. The total doses of NMU given to the various treatment groups were 15, 12, 9, 6, 3 and 1.5 mg 100 g body weight. Tumor incidence ranged from approximately 100 to 0% in the control and reserpine-treated groups, depending on the dose of carcinogen given. Concurrent reserpine administration with the NMU decreased the number of tumors per rat; at 15 and 12 mg 100 g body weight NMU doses the values were only 58 and 55% of the respective controls. Reserpine treatment at these 2 NMU doses also increased the percentage of well-differentiated mammary tumors compared with corresponding controls. Tumor estrogen receptor levels in controls ranged from 71 to 78 fmol/mg protein and in the reserpine-treated groups from 96 to 105 fmol/mg protein; significant elevations were present in the rats given reserpine and the 2 highest doses of NMU. Tumor progesterone and prolactin receptor levels were similar in control and reserpine-treated groups. The estrous cycle of the controls was frequently arrested at estrus and 21 57 (37%) had a fluid-distended uterus and thickened uterine walls; only 2 52 (4%) of reserpine-treated rats had hydrometria and none exhibited cycle arrest at estrus. The effect of reserpine on mammary tumors was also studied when given after initial exposure to the carcinogen. NMU was administered to 65 rats in 3 doses of 5 mg 100 g body weight by i.v. injections 4 weeks apart. Equal numbers of animals comprised 1 control and 2 reserpine treatment groups. Reserpine was given at a daily dose of 20 μg 100 g body weight commencing 67 days after the first NMU dose (chronic regimen) or by the same schedule preceded by 50 μg 100 g doses given on the day before, with and on the day after the second and third NMU injections (acute/chronic regimen). A fourth group of rats received chronic reserpine treatment but no NMU. All 3 NMU-exposed groups had a 100% tumor incidence; none developed in the reserpine-treated controls. The acute/chronic reserpine treatment increased the rate of tumor development but neither drug schedule altered the number of tumors per rat or the mean final total tumor areas. Reserpine administration was associated with greater degrees of anaplasia in mammary tumors induced by NMU ( P < 0.01). The mean tumor estrogen receptor content was significantly higher in the acute/chronic reserpine-treated group ( P < 0.0002) and the chronic reserpine-treated animals ( P < 0.008) compared with controls. Tumor prolactin receptor content was unaffected by the drug. Peroxidase activity was higher in mammary tumors and lower in uteri from reserpine-treated rats compared with tumor-bearing controls. Also, there was a strong correlation ( r = 0.82) between the mammary tumor estrogen receptor and tumor peroxidase activity for rats treated with the acute/chronic reserpine regimen.
Published Version
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