Stage-specific inhibition of mammary carcinogenesis by 1alpha-hydroxyvitamin D5.
Stage-specific inhibition of mammary carcinogenesis by 1alpha-hydroxyvitamin D5.
复制标题
1α-羟基维生素 D5 对乳腺癌发生的阶段特异性抑制。
DOI：
10.1016/j.ejca.2004.05.025
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Mehta,RajendraG
中科院分区：
文献类型：
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作者：
Mehta,RajendraG
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.
