Strategy of research for cancer—chemoprevention

Abstract

It has been reported that environmental chemicals are important factors in terms of both development and prevention of human cancer. For the latter, detection of early stages is an essential first step followed by clinical trials for surveying populations at risk. Thus a great deal of attention has been focused on these areas. However, investigations of possibilities for active prevention of cancer development itself form another major project. Chemoprevention of carcinogenesis, which means prevention of carcinogenesis by exogenous chemical compounds, has been investigated extensively in a variety of organs in animal models. Usually attention is concentrated on only one organ. However, antioxidants, such as BHA, exert very different effects on different organs, suggesting the necessity of whole body approaches to the question of chemoprevention. Furthermore, the mechanisms of chemoprevention, including the step of carcinogenesis, i.e., initiation, promotion, progression or whole carcinogenesis steps, in which exogenous compounds exert their protective effects, should be considered. A medium-term bioassay system and a multi-organ carcinogenesis system, which can be used for investigation of potential for cancer chemoprevention, have been developed in our laboratory. Dose dependent inhibitory effects were established for both BHA and alpha-tocopherol in the medium-term bioassay system, and inhibition of small intestinal carcinogenesis by catechins in green tea has also been investigated in our multi-organ carcinogenesis protocol. It is extremely important for prevention of human cancer that we find new candidates for chemopreventive agents using animal studies. This paper reviews published reports on chemoprevention, taking into account effective stages, and proposes suitable experimental animal models for future investigations in this increasingly important area.

Inhibitory effects of phenolic compounds on development of naturally occurring preneoplastic hepatocytic foci in long-term feeding studies using male F344 rats

“…However, foci of altered hepatocytes, considered to be preneoplastic lesions, are often present in aged rats [11][12][13][14], so chemopreventive agents might be expected to reduce their size or numbers. With regard to the human risk of hepatocarcinogenicity in individuals consuming phenolic compounds for long periods, no adequate data have been reported [15,16].…”

Phytochemicals: A Glimpse into their Structural and Biological Variation

“…The ingestion of fruits and vegetables may lead to a protective effect in the occurrence of human cancer, due not only to flavonoids but also due to other phytochemicals such as chlorophyllin, indoles, isothiocyanates, sterols, phenols, protease inhibitors, and vitamins present in plants (Ito and Imaida, 1992). In terms of their potential mediation of cancer chemoprevention, flavonoids have been shown to interact in the genesis of cancer in all of its various stages of initiation, promotion, and progression (Ito and Imaida, 1992).…”

“…The ingestion of fruits and vegetables may lead to a protective effect in the occurrence of human cancer, due not only to flavonoids but also due to other phytochemicals such as chlorophyllin, indoles, isothiocyanates, sterols, phenols, protease inhibitors, and vitamins present in plants (Ito and Imaida, 1992). In terms of their potential mediation of cancer chemoprevention, flavonoids have been shown to interact in the genesis of cancer in all of its various stages of initiation, promotion, and progression (Ito and Imaida, 1992). For example, these compounds have been shown to block the promotion stage of carcinogenesis, and inhibit ornithine decarboxylase (ODC) synthesis, alter hormonal balance and cause the reduction of free radicals (Fujiki et al, 1986;Hatano et al, 1988;Fujita et al, 1989;Huang et al, 1992).…”

Alternative Multiorgan Initiation–Promotion Assay for Chemical Carcinogenesis in the Wistar Rat

“…A multiorgan 28-weeklong system based on the mechanistic initiation–promotion concept of chemical carcinogenesis was proposed by a research group led by Nobuyuki Ito at the Nagoya City University Medical School, Japan, as an alternative/complementary approach to the conventional long-term bioassay system (Ito et al 1996, 1988; Shirai, Hirose, and Ito 1999; Ito and Imaida 1992; Ito et al 1998). It consists of sequential treatment of rats with five genotoxic carcinogens to establish multiorgan initiation of carcinogenesis followed by dietary exposure to a test substance in order to evaluate its promoting potential.…”