Stage-specific inhibition of mammary carcinogenesis by 1α-hydroxyvitamin D5

• Published in: European journal of cancer (1990) Vol. 40; no. 15; pp. 2331 - 2337
• Main Author: Mehta, Rajendra G.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.10.2004; Elsevier
• Subjects: Biological and medical sciences; Chemoprevention; Mammary carcinogenesis; Medical sciences; Organ culture; Pharmacology. Drug treatments; Preneoplastic lesions; Tumors; Vitamin D analogue; D5; Preneoplastic lesions; Chemoprevention; Vitamin D analogue; Organ culture; Mammary carcinogenesis; Chemoprophylaxis; Premalignant lesion; Pharmacology; Carcinogenesis; Prevention; Chemotherapy; Cancerology; Vitamin D; Inhibitor; Mammary gland
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2004.05.025

Active metabolites of vitamin D are well recognised as cancer chemopreventive and chemotherapeutic agents. However, they are toxic at effective concentrations. Earlier, we reported that a non-toxic analogue of vitamin D, 1α-hydroxyvitamin D5(1α(OH)D5), inhibited carcinogen-induced mammary lesion formation in mouse mammary organ cultures (MMOC) and in N-methyl- N-nitrosourea (MNU)-induced rat mammary carcinogenesis. In the present study, we determined if 1α (OH)D5 action is selective during the initiation or promotion phases in MMOC and in vivo. In MMOC, 1 μM 1α (OH)D5 suppressed both ovarian hormone-dependent and -independent mammary lesions by more than 60%. Inhibition of alveolar lesions was observed only during the promotion stage ( p = 0.0016). In a 7,12-dimethylbenz( a)anthracene (DMBA)-induced mammary carcinogenesis experiment, 1α (OH)D5 (40 μg/kg diet) inhibited cancer incidence by 37.5% ( p < 0.05) if 1α (OH)D5 was present in food during the promotion phase (+1 to end). However, a D5-supplemented diet during the initiation phase (−2 to +1 week) did not provide any protection. These results clearly show, for the first time, that the effects of vitamin D may be mediated selectively during the promotion or progression phases of carcinogenesis.