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The nongenotoxic carcinogens naphthalene and para-dichlorobenzene suppress apoptosis in Caenorhabditis elegans.

Abstract：

:Naphthalene (1) and para-dichlorobenzene (PDCB, 2), which are widely used as moth repellents and air fresheners, cause cancer in rodents and are potential human carcinogens. However, their mechanisms of action remain unclear. Here we describe a novel method for delivering and screening hydrophobic chemicals in C. elegans and apply this technique to investigate the ways in which naphthalene and PDCB may promote tumorigenesis in mammals. We show that naphthalene and PDCB inhibit apoptosis in C. elegans, a result that suggests a cellular mechanism by which these chemicals may promote the survival and proliferation of latent tumor cells. In addition, we find that a naphthalene metabolite directly inactivates caspases by oxidizing the active site cysteine residue; this suggests a molecular mechanism by which these chemicals suppress apoptosis. Naphthalene and PDCB are the first small-molecule apoptosis inhibitors identified in C. elegans. The power of C. elegans molecular genetics, in combination with the possibility of carrying out large-scale chemical screens in this organism, makes C. elegans an attractive and economic animal model for both toxicological studies and drug screens.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

Kokel D,Li Y,Qin J,Xue D

doi

10.1038/nchembio791

subject

Has Abstract

pub_date

2006-06-01 00:00:00

pages

338-45

issue

6

eissn

1552-4450

issn

1552-4469

pii

nchembio791

journal_volume

2

pub_type

杂志文章

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