#C158 Suppression of Mammary Gland Carcinogenesis by Post-Initiation Treatment of Rats with Tamoxifen or Indole-3-Carbinol or their Combination. Danuta Malejka-Giganti,1 Gloria A. Niehans,1 Kristen K. Bennett,1 Daniel R. Parkin,1 Richard W. Decker,2 Robin L. Bliss.2 Veterans Affairs Medical Center,1 Minneapolis, MN, University of Minnesota,2 Minneapolis, MN. A more effective inhibition of growth of human MCF-7 breast cancer cells was achieved with a combination of tamoxifen (TAM) and indole-3-carbinol (I3C) than with either agent alone (Cover et al Cancer Res 59: 1244, 1999). Our study examined the post-initiation effects of TAM, I3C or TAM+I3C on mammary gland tumorigenesis induced in seven week-old female Sprague-Dawley rats with one oral dose of 7,12-dimethylbenz[a]anthracene (DMBA) at 65 mg/kg of body weight (bw). Starting two weeks after DMBA, rats were treated with TAM (10 micro-molar/rat) or 10% ethanol in olive oil (Veh I at 50 micro-molar L/rat) by s.c. injections, and/or with I3C (250 mg/kg bw) or 20% ethanol in olive oil (Veh II at 2.5 mL/kg bw) by oral gavages, three times per week, for up to 20 weeks. Four groups included: 1) Veh I+Veh II (n=21)-; 2) TAM+Veh II (n=18)-; 3) Veh I+I3C (n=19)-; and 4) TAM+I3C (n=23)-treated rats. Since all tumors in group 1 and the majority of those in groups 2, 3 and 4 were malignant (mammary adenocarcinomas and ductal carcinomas in situ), statistical analyses of tumor incidence and latency, multiplicity and mass concerned malignant tumors only. The median latent period of tumors was 72, 119, 70 and 112 days in groups 1, 2, 3 and 4, respectively. Since the differences between groups 2 and 1 (P=0.0023), 4 and 1 (P=0.0008), and 4 and 3 (P=0.0356) were significant, the observed suppression of mammary carcinogenesis through the increased tumor latency was due to TAM. At 112 days after DMBA, the estimated malignant tumor incidences were 84, 46, 65 and 51% in groups 1, 2, 3 and 4, respectively. The mean number of malignant tumors per rat ± SD in group 2 (0.94 &/-0.94), 3 (1.47 &/-1.02) or 4 (0.61 &/-0.72) was significantly different (P=0.0007, P=0.0493 or P<0.0001, respectively) from that in group 1 (2.24 &/- 1.48), and that between group 4 and 3 was also different (P=0.0014). Likewise, the mean number of malignant tumors per tumor (malignant+benign)-bearing rat &/- SD in group 2 (1.42 &/-0.79), 3 (1.75 &/-0.86) or 4 (1.08 &/-0.64) was significantly different (P=0.0009, P=0.0145 or P<0.0001, respectively) from that in group 1 (2.61 &/- 1.24), and that between group 4 and 3 was also different (P=0.0122). Thus, the decrease in malignant tumor multiplicity achieved by treatment of rats with TAM was greater than that with I3C, and TAM in combination with I3C amplified the decrease effected by the latter. The mean tumor weight (g) per rat ± SD for group 2 (0.49 &/-0.65) or 4 (0.59 &/-1.47) was statistically different (P=0.0251 or P=0.0034, respectively) from that of group 1 (1.55 &/-;1.93), and that of group 4 was also different (P=0.0338) from group 3 (0.79±1.07). Hence, the decrease in malignant tumor weight was achieved only by treatment of rats with TAM. In conclusion, post-initiation treatment of rats with TAM at very low doses effectively suppresses mammary gland carcinogenesis as shown by the increase in malignant tumor latency and decreases in tumor multiplicity and mass. The suppressing effect of I3C alone is limited to the decrease in the malignant tumor multiplicity, and this is enhanced by co-treatment with TAM. Importantly, administration of I3C at the dose level that maintains upregulation of oxidative metabolism of 17 beta-estradiol and estrone in the liver, does not diminish the suppressing effects of TAM on mammary carcinogenesis. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.