Circadian rhythm of tumor promotion in the two-stage model of mouse tumorigenesis

• Published in: Cancer letters Vol. 190; no. 2; pp. 143 - 149
• Main Author: Wille, John J.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 20.02.2003; Elsevier; Elsevier Limited
• Subjects: 12- 0-tetradecanoyl-phorbol acetate; 9,10-Dimethyl-1,2-benzanthracene - administration & dosage; 9,10-Dimethyl-1,2-benzanthracene - pharmacology; Animals; Biological and medical sciences; Cancer; Carcinogenesis; Cell cycle; Circadian Rhythm; Circadian rhythms; Deoxyribonucleic acid; Disease Models, Animal; DNA; Medical sciences; Mice; Retinoic acid; Skin Neoplasms - chemically induced; Skin Neoplasms - pathology; Studies; Tetradecanoylphorbol Acetate - administration & dosage; Tetradecanoylphorbol Acetate - pharmacology; Time Factors; Tumor promotion; Tumorigenesis; Tumors; Circadian rhythms; Carcinogenesis; Retinoic acid; Tumor promotion; 12- 0-tetradecanoyl-phorbol acetate; 12-0-tetradecanoyl-phorbol acetate
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(02)00594-3

The question of whether cancer risk is influenced by time-of-day exposure to potentially carcinogenic agents was approached in this study by exposing mouse skin to a single initiating dose of 7,12-dimethylbenz [∀-]anthracene, followed by a 12 week regime of bi-weekly skin treatments with the tumor promoter, 12- 0-tetradecanoyl-phorbol acetate (TPA), given at four different circadian clock times (CCTs). Tumor incidence, average number of tumors per mouse and tumor size showed a dominant circadian component with an acrophase occurring at 23:00 h CCT. Pre-treatment with all trans-retinoic acid, prior to bi-weekly TPA promotion, reduced tumor incidence, average number and size of tumors per animal by greater than 80%, but did not suppress the underlying circadian rhythm of sensitivity to TPA-induced tumor formation.