Chemical carcinogenesis, multistage process

CTAs are possible in vitro alternatives to the standard approach for the assessment of carcinogenicity (the 2-year bioassay in rodents), which have been shown to be a multistage process able to model the most important stages of in vivo carcinogenesis [50]. CTAs are faster and more economic than in vivo assay and they could be a valid and useful screening tool for chemicals. 

Initiation-Promotion Studies. Carcinogenesis has been demonstrated to be a multistage process in the cells of certain animal tissues, including skin. lung, liver, and bladder. This process is believed to occur in human tumorigenesis as well. The PAHs have been studied extensively for their ability to act as tumor initiators and/or promoters. Following is a brief discussion, by chemical, ofthe results of the initiation-promotion studies performed with 13 of the 17 PAHs discussed in this profile. Only those studies considered adequate and reliable are presented in Table 2- 3. 

The mechanism of chemical carcinogenesis involves a complex multistage process that occurs in certain distinct phases. While genotoxic carcinogens manifest their actions in three phases (1) initiation, (2) promotion, and (3) progression, the mechanisms for nongenotoxic carcinogen can vary and are more complex. The routes of exposure, dose amount, absorption, and distribution of the chemical within the body as well as the nature of the metabolic products, play important roles in the process. 

Mechanistic understanding is especially crucial for (Q)SAR analysis/modeUng of chemical carcinogens because of the complexity and multistage, multifactorial process of carcinogenesis (see discussion below). The importance of mechanistic considerations in (Q)SAR analysis of chemical carcinogens has been discussed by Woo and Lai (2003). Mechanistic considerations can improve (Q)SAR study by... 

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