Issues in Risk Assessment (1993) / Chapter Skim
Currently Skimming:
THE TWO-STAGE MODEL
THE TWO-STAGE MODEL
Pages 190-195
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 190... ...
It explicitly accounts for many processes considered important in carcinogenesis, including cell division, mutation, differentiation, and death and the clonal expansion of populations of cells. Although the various carcinogenic processes might have more than two steps, a major assumption is that each of them can be described as consisting of two critical, genomic events: the first is assumed to give a small growth advantage through partial abrogation of growth control, and the second is assumed to lead to total abrogation of growth control.
|
From page 191... ...
, C0, C1, C2, and D represent stem cells, intermediate cells, malignant cells, and differentiated or dead cells. A normal stem cell can divide into two stem cells, die, or be transformed by mutation into an altered intermediate cell.
|
From page 192... ...
Please use the print version of this publication as the authoritative version for attribution. is generally modeled as growing deterministically, with intermediate cells arising from normal cells in a nonhomogeneous Poisson process with intensity function X(s)
|
From page 193... ...
Intermediate cells behave independently and with exponentially distributed lifespans. Consequently, clones of intermediate cells either die out or increase exponentially in size; there is no provision for growth regulation.
|
From page 194... ...
One of the most important applications of dose-response models in risk assessment is to predict increased risk from exposure to low doses of a chemical. Typically, increased cancer risks on the order of 1/100 cannot be accurately measured in either a standard animal bioassay or an epidemiologic study due to limitations of sample size, yet increased risks in human populations of this magnitude, and even smaller, are of concern.
|
From page 195... ...
This assumption implies that adenomas progress to carcinomas and is open to investigation. Generally, the two-stage model is more useful than mainly descriptive models for testing mechanistic hypotheses of this type, because several models can be developed based on alternative biologic hypotheses, which can then be tested on the basis of goodness-of-fit.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.