Caffeine (1,3,7-trimethylxanthine) holds the dubious distinction of being the most widely used psychotropic drug in North America. The methylated purine is most often consumed in colas, teas, chocolates and numerous prescription and non-prescription drugs. Despite the ubiquitous consumption of the drug, we still do not know whether or not the drug is an important contributing """"""""lifestyle"""""""" factor in the genesis of malignant disease. Such is the case with human breast tumors (benign and malignant); controversy still exists as to whether or not caffeine consumption contributes to human breast tumorigenesis. During the past 3 years, our studies provide evidence that caffeine consumption (via the drinking water) can indeed effect (inhibit and enhance) mammary gland tumorigenesis in experimental animals, a phenomenon that is dependent upon the time-span of caffeine treatment, the dose of caffeine used and the animal model examined. In this research proposal, we intend to further examine the role of caffeine in experimental animal (rat and mouse) mammary gland tumorigenesis. Specifically, we intend to: 1) further evaluate the role of caffeine in DMBA-induced rat mammary gland tumorigenesis and, in addition, examine the role of caffeine in the MNU-induced rat mammary carcinoma model and in the pregnancy- and hormone-induced mouse mammary carcinoma model. In addition, we intend to: 2) examine the influence of caffeine on normal mammary gland developmental growth processes in immature and mature mice and 3) determine the influence of caffeine on mammotropic hormone secretion in immature and mature rats. These studies are designed to extend our current understanding of the influence of caffeine on normal and neoplastic mammary gland developmental growth processes and provide insight into the mechanism by which the drug influences these processes.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA037613-04
Application #
3175387
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1984-07-01
Project End
1993-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Michigan State University
Department
Type
Schools of Medicine
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Welsch, C W; VanderPloeg, L C (1994) Enhancement by caffeine of mammary gland lobulo-alveolar development in mice: a function of increased corticosterone. J Environ Pathol Toxicol Oncol 13:81-8
Welsch, C W (1994) Caffeine and the development of the normal and neoplastic mammary gland. Proc Soc Exp Biol Med 207:1-12
VanderPloeg, L C; Wolfrom, D M; Rao, A R et al. (1992) Caffeine, theophylline, theobromine, and developmental growth of the mouse mammary gland. J Environ Pathol Toxicol Oncol 11:177-89
Wolfrom, D M; Rao, A R; Welsch, C W (1991) Caffeine inhibits development of benign mammary gland tumors in carcinogen-treated female Sprague-Dawley rats. Breast Cancer Res Treat 19:269-75
VanderPloeg, L C; Welsch, C W (1991) Inhibition by caffeine of ovarian hormone-induced mammary gland tumorigenesis in female GR mice. Cancer Lett 56:245-50
VanderPloeg, L C; Wolfrom, D M; Welsch, C W (1991) Influence of caffeine on development of benign and carcinomatous mammary gland tumors in female rats treated with the carcinogens 7,12-dimethylbenz(a)anthracene and N-methyl-N-nitrosourea. Cancer Res 51:3399-404
Wolfrom, D; Welsch, C W (1990) Caffeine and the development of normal, benign and carcinomatous human breast tissues: a relationship? J Med 21:225-50
Welsch, C W; DeHoog, J V; O'Connor, D H (1988) Influence of caffeine consumption on carcinomatous and normal mammary gland development in mice. Cancer Res 48:2078-82
Welsch, C W; DeHoog, J V (1988) Influence of caffeine consumption on 7,12-dimethylbenz(a)anthracene-induced mammary gland tumorigenesis in female rats fed a chemically defined diet containing standard and high levels of unsaturated fat. Cancer Res 48:2074-7
Welsch, C W; DeHoog, J V; O'Connor, D H (1988) Influence of caffeine and/or coffee consumption on the initiation and promotion phases of 7,12-dimethylbenz(a)anthracene-induced rat mammary gland tumorigenesis. Cancer Res 48:2068-73

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