Page 195 - Vitamin D and Cancer

182 S.A. Mazzilli et al.

containing either 0, 25, or 50 mg/kg 1a (OH)D /diet beginning 2 weeks prior to
5
MNU injections and followed for an additional 120 days. These studies demonstrated
that 1a (OH)D reduced both tumor incidence by 26.7% and 33.4% and tumor
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multiplicity by 25% and 50% in the 25 and 50 mg/kg 1a (OH)D /diet groups
5
respectively as compared to the untreated group. To examine the stage specific
effects, three treatment cohorts were created all of which received 40 mg/kg 1a
(OH)D in the diet beginning at the following times: I. prior to initiation/promotion
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at 2 weeks prior to DMBA treatment; II. during initiation at the time of DMBA; or
III. during promotion at 1 week post DMBA treatment. A fourth group was treated
with rat chow containing no 1a (OH)D . The results of this study demonstrated no
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significant effects of 1a (OH)D in the diet during the initiation phase; however,
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tumor incidence was reduced by 37.5% in rats receiving 1a (OH)D during the
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promotional stage.
To further investigate vitamin D’s chemopreventive effect, Zinser et al. con-
ducted a study to examine the role of 1,25(OH) D on mammary gland development
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during puberty [27]. After demonstrating that VDR was present in a number of
mouse mammary cell lines the authors compared the mammary development in
−/−
VDR mice on a high calcium diet to VDR wt/wt mice. The study showed that the
mammary glands in the VDR mice were heavier, had enhance ductal growth and
−/−
increased secondary branch points and had an increased number of terminal end
buds compared to the VDR wt/wt mice.
Overall the examination of vitamin D in the diet and the administration of
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1,25(OH) D or its analogs demonstrated a reduction in tumor incidence in a num-
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ber of animal models. Additionally, the illustration that 1,25(OH) D is involved in
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the control of mammary gland growth and development furthers the rationale that
vitamin D may be useful in altering the course of mammary tumorigenesis.
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Together these studies provide rationale for continued exploration into the clinical
application for vitamin D as a chemopreventive agent to potentially reduce the
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incidence and mortality of breast cancer.

8.2.4 Lung Cancer

There are currently no published studies examining the preventive effects of dietary
vitamin D in lung cancer animal models. However, Mernitz et al. examined the
3
active metabolite, 1,25(OH) D for its potential to inhibit lung carcinogenesis in the
2
3
4-(methynitrosamino)-1-(3-pyridyl)-1-butanone (NNK) carcinogen-induced animal
model [28]. The mice in this study were fed a diet with 2.5, or 5 mg 1,25(OH) D /kg
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2
diet (0.5 and 1.0 mg 1,25(OH) D /kg body weight/day) for 20 weeks. A single
2
3
administration of 100 mg/kg body weight of NNK was injected 3 weeks from the
start of the 1,25(OH) D diet. Following 20 weeks on the diet, the lungs of treated
2
3
animals were analyzed and lung lesions were quantified to determine the incidence
and multiplicity of pulmonary surface tumors. Lung tumor incidence was reduced
by 36% in the mice treated with 2.5 mg/kg diet of 1,25(OH) D and by 82% in those
2 3