Carcinogenesis Advance Access published online on March 3, 2005
Carcinogenesis, doi:10.1093/carcin/bgi051
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1 Department of Food Science and Human Nutrition, Iowa State University, Ames, IA 50011
* To whom correspondence should be addressed. Our laboratory has demonstrated previously that dietary energy restriction (DER) inhibited the promotion of skin tumorigenesis and others have found that adrenalectomy may reverse that inhibition. The purpose of the research reported here was to determine if circulating corticosterone (CCS) may be the adrenal hormone responsible for DER prevention of skin carcinogenesis. Female Sencar mice were initiated with 7,12-dimethylbenzanthracene (DMBA) and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA) in either sham-operated or adrenalectomized (ADX) mice fed ad libitum (AL) or dietary energy restricted (DER) diets. DER was 60% of the AL calorie intake with the removal of energy from fat and carbohydrate. CCS, the main glucocorticoid hormone secreted by the murine adrenal gland, was added to the drinking water of AL/ADX and DER/ADX groups to determine the involvement of CCS in the DER inhibition of tumor development. In sham-operated groups, DER compared to AL fed mice experienced significantly decreased papilloma incidence and multiplicity (P < 0.0001). ADX did not alter papilloma incidence or multiplicity in AL fed mice but ADX partially reversed the inhibition of papilloma multiplicity and incidence in DER mice. CCS supplementation to both DER/ADX and AL/ADX mice resulted in reduced papilloma incidence and multiplicity. In DER/ADX mice, CCS dramatically reduced papilloma rates while in AL/ADX mice CCS reduced the papilloma rates to those seen in the DER sham group. DER significantly reduced carcinoma multiplicity mean counts per effective animal (P < 0.0001) compared to AL fed groups in sham and ADX/CCS groups. DER/ADX mice lost the carcinoma multiplicity protection seen in sham DER mice. CCS treatment of ADX mice significantly decreased total carcinoma (insitu and invasive) incidence rates per effective animal (P < 0.0003). ADX plus CCS treatment in the DER mice resulted in the lowest carcinoma incidence and multiplicity. Thus, DER inhibition of skin tumorigenesis was mediated at least in part through CCS. However, CCS was more effective in preventing papillomas and carcinomas in DER/ADX mice than in AL/ADX mice, suggesting that other factors may also be involved in the DER prevention of tumor formation.
Received October 4, 2004
Revised February 1, 2005
Accepted February 8, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Prevention of mouse skin tumor promotion by dietary energy restriction requires an intact adrenal gland and glucocorticoid supplementation restores inhibition
2 Department of Statistics, Iowa State University, Ames, IA 50011
3 Department of Veterinary Pathology, Iowa State University, Ames, IA 50011
Diane F. Birt, E-mail: dbirt{at}iastate.edu
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