Environmental Health Perspectives 105, Supplement 4, June 1997: Article by Stoner et al.

Perspectives in Cancer Chemoprevention

Gary D. Stoner,¹ Mark A. Morse,¹ and Gary J. Kelloff²

¹Arthur James Cancer Hospital and Research Institute, The Ohio State University, Columbus, Ohio; ²National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Abstract
Cancer chemoprevention can be defined as prevention of cancer by the administration of one or more chemical entities, either as individual drugs or as naturally occurring constituents of the diet. Based largely on the time period that chemopreventive agents exhibit activity in animal models of carcinogenesis, they can be classified as inhibitors of carcinogen formation, blocking agents, and suppressing agents. The majority of compounds that inhibit the formation of carcinogens prevent the formation of nitrosamines from secondary amines and nitrite in an acidic environment. Blocking agents are inhibitors of tumor initiation, while suppressing agents are inhibitors of tumor promotion/progression. Many well-characterized chemopreventive agents act at one or more steps in both tumor initiation and promotion/progression. The objective of this paper is to provide a general discussion of the mechanisms through which chemopreventive agents inhibit carcinogenesis. Examples of agents that act through these mechanisms are given; however, a complete listing of effective chemopreventive agents is not possible within the context of this paper. At the conclusion is a brief discussion of future prospects in cancer chemoprevention and obstacles to overcome. -- Environ Health Perspect 105(Suppl 4):945-954 (1997)

Key words: cancer, chemoprevention, mechanisms, anti-initiation, antipromotion, antiprogression

This paper is based on a presentation at the symposium on Mechanisms and Prevention of Environmentally Caused Cancers held 21-25 October 1995 in Santa Fe, New Mexico. Manuscript received at EHP 16 April 1996; accepted 16 August 1996.

Portions of this research were supported by National Institutes of Health grants CA 28950 and CA 46535.

Address correspondence to Dr. G.D. Stoner, The Ohio State University, Arthur James Cancer Hospital and Research Institute, Room 1148, 300 W. Tenth Avenue, Columbus, OH 43210. Telephone: (614) 293-3268. Fax: (614) 293-3333. E-mail: stoner.21@osu.edu

Abbreviations used: AAF, 2-acetylaminofluorene; ADPRT, poly(ADP-ribosyl)transferase; BPDE, benzo[a]pyrene diol epoxide; BHA, butylated hydroxyanisole; DFMO, -difluoromethylornothine; DMBA, 7,12-diemthylbenz[a]anthrancene; FDA, U.S. Food and Drug Administration; GST, glutathione S-transferase; 13C, indole-3-carbinol; IGF-I, insulinlike growth factor I; MNU, methylnitrosourea; NAC, N-acetylcysteine; NCI, National Cancer Institute; NMBA, N-nitrosomethylbenzylamine; NK, natural killer; NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; NSAID, nonsteroidal anti-inflammatory drug; ODC, ornithine decarboxylase; PKC, protein kinase C; TGF-ß, transforming growth factor ß; TPA, 12-O-tetradecanoylphorbol-13-acetate; UDC, urine diphosphate.

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Last Update: June 27, 1997