International Development, Community, and Environment

Title

A Preliminary Operational Classification System for Nonmutagenic Modes of Action for Carcinogenesis

Document Type

Article

Abstract

This article proposes a system of categories for nonmutagenic modes of action for carcinogenesis. The classification is of modes of action rather than individual carcinogens, because the same compound can affect carcinogenesis in more than one way. Basically, we categorize modes of action as: (1) co-initiation (facilitating the original mutagenic changes in stem and progenitor cells that start the cancer process) (e.g. induction of activating enzymes for other carcinogens); (2) promotion (enhancing the relative growth vs differentiation/death of initiated clones (e.g. inhibition of growth-suppressing cell-cell communication); (3) progression (enhancing the growth, malignancy, or spread of already developed tumors) (e.g. suppression of immune surveillance, hormonally mediated growth stimulation for tumors with appropriate receptors by estrogens); and (4) multiphase (e.g., "epigenetic" silencing of tumor suppressor genes). A priori, agents that act at relatively early stages in the process are expected to manifest greater relative susceptibility in early life, whereas agents that act via later stage modes will tend to show greater susceptibility for exposures later in life. Copyright © 2008 Informa UK Ltd.

Publication Title

Critical Reviews in Toxicology

Publication Date

2-1-2009

Volume

39

Issue

2

First Page

97

Last Page

138

ISSN

1040-8444

DOI

10.1080/10408440802307467

Keywords

cancer, initiation, mechanisms, progression, promotion

Disciplines

Medicine and Health | Social and Behavioral Sciences | Sociology

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