C A NC ER LETTERS Cancer Letters 86 (1994) 223-228 Induction of mammary tumors in rat by intraperitoneal injection of NMU: histopathology and estral cycle influence E.S. Riveraa, N. Andradeb, G. Martin”, G. Melitoa, G. Cricco”, N. Mohamada, C. Davioa, R. Caroa, R.M. Bergoc*a zyxwvutsrqponmlkjihgfedcbaZYXW ‘Laboratorio de Radioisdtopos, Gtedra de Fisica, Faculiad de Farmacia y Bioquimica. Universidad de Buenos Aires, Junin 965, 1113 Buenos Aires, Argentina bInsrituto de Oncologia ‘Angel H. Roffo”. Facultad de Medicina. Universidad de Buenos Aires, Buenos Aires, Argentina Received 10 June 1994; revision received 9 September 1994; accepted 16 September 1994 zyxwvutsrqponmlkjihgfedcb Abstract In order to obtain an experimental model we induced mammary tumors in female Sprague-Dawley rats. The car- cinogen N-nitroso-N-methylurea (NMU) was injected intraperitoneally (i.p.) at doses of 50 mg/kg body weight when animals were 50, 80 and 110 days old. Tumor sizes were measured with a caliper and their growth parameters and histopathological properties were tested. For 100 rats, 88.4% of developed lesions were ductal carcinomas, histological- ly classified as 52.8% cribiform variety, 30.6% solid carcinoma. Metastases in liver, spleen and lung were present. Other primary tumors were detected with low incidence. The influence of the rat estrous cycle during the first exposure to intraperitoneal NMU injection was studied. The latency period in estrus, proestrus and diestrus was 82 f 15, 77 f 18 and 79 f 18 days, respectively. Tumor incidence was significantly higher in estrus (95.2%) than proestrus (71.4%) or diestrus (77.4), (P < 0.01). Mean number or tumors per animal was similar among the three groups (4.4 + 3.2, 3.8 f 3.6, 3.2 f 1.8). The procedure described appears to be the simplest method for inducing experimental mammary tumors in rats. Keywords: N-Nitroso-N-methylurea; Carcinogenesis; Mammary tumors; Rats zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQ 1. Introduction Mammary tumors can be induced in rats by different methods such as chemical carcinogens [16] and ionizing radiation [ll]. With Huggin’s description [ 161 of induction of mammary gland tumors in rats by a single dose of 7,12-dimethyl- benzo[a]anthracene (DMBA), a period of produc- tive investigation on mammary gland carcino- genesis began. This chemical agent, as well as irra- diation, induces principally benign tumors like Abbreviations: DMBA, 7,12-dimethylbenzo[a]antracene; NMU, N-nitroso-N-methylurea; TEB, Terminal end bud. * Corresponding author. papillomas with hyperplastic and dysplastic epithelia and also malignant lesions with low metastasis frequency. 0304-3835/94/$07.00 0 1994 Elsevier Science Ireland Ltd. All rights reserved SSDI 0304-3835(94)03567-3