Transcriptional changes associated with reduced spontaneous liver tumor incidence in mice chronically exposed to high dose arsenic.
Exposure of male C3H mice in utero (from gestational days 8-18) to 85ppm sodium arsenite via the dams' drinking water has previously been shown to increase liver tumor incidence by 2 years of age. However, in our companion study (Ahlborn et al., 2009), continuous exposure to 85ppm sodium arsenic (from gestational day 8 to postnatal day 365) did not result in increased tumor incidence, but rather in a significant reduction (0% tumor incidence). The purpose of the present study was to examine the gene expression responses that may lead to the apparent protective effect of continuous arsenic exposure. Genes in many functional categories including cellular growth and proliferation, gene expression, cell death, oxidative stress, protein ubiquitination, and mitochondrial dysfunction were altered by continuous arsenic treatment. Many of these genes are known to be involved in liver cancer. One such gene associated with rodent hepatocarcinogenesis, Scd1, encodes stearoyl-CoA desaturase and was down-regulated by continuous arsenic treatment. An overlap between the genes in our study affected by continuous arsenic exposure and those from the literature affected by long-term caloric restriction suggests that reduction in the spontaneous tumor incidence under both conditions may involve similar gene pathways such as fatty acid metabolism, apoptosis, and stress response.
Nelson
Gail M
GM
United States Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711, United States.
Ahlborn
Gene J
GJ
Allen
James W
JW
Ren
Hongzu
H
Corton
J Christopher
JC
Waalkes
Michael P
MP
Kitchin
Kirk T
KT
Diwan
Bhalchandra A
BA
Knapp
Geremy
G
Delker
Don A
DA
D000367:Age Factors; D000375:Aging / Q000235:genetics; D000818:Animals; D018053:Arsenites / Q000008:administration & dosage; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D005865:Gestational Age; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017670:Sodium Compounds / Q000008:administration & dosage; D014158:Transcription, Genetic
D018053:Arsenites; D017670:Sodium Compounds; C017947:sodium arsenite