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Arsenic, mode of action at biologically plausible low doses: what are the implications for low dose cancer risk?

Abstract：

:Arsenic is an established human carcinogen. However, there has been much controversy about the shape of the arsenic response curve, particularly at low doses. This controversy has been exacerbated by the fact that the mechanism(s) of arsenic carcinogenesis are still unclear and because there are few satisfactory animal models for arsenic-induced carcinogenesis. Recent epidemiological studies have shown that the relative risk for cancer among populations exposed to 10 microM), As induces down-regulation of DNA repair, oxidative DNA damage and apoptosis. This low dose adaptive (protective) response by a toxic agent is known as hormesis and is characteristic of many agents that induce oxidative stress. A mechanistic model for arsenic carcinogenesis based on these data would predict that the low dose risk for carcinogenesis should be sub-linear. The threshold dose where toxicity outweighs protection is hard to predict based on in vitro dose response data, but might be estimated if one could determine the form (metabolite) and concentration of arsenic responsible for changes in gene regulation in the target tissues.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Snow ET,Sykora P,Durham TR,Klein CB

doi

10.1016/j.taap.2005.01.048

subject

Has Abstract

pub_date

2005-09-01 00:00:00

pages

557-64

issue

2 Suppl

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(05)00326-1

journal_volume

207

pub_type

杂志文章,评审

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