Inhalant nitrite exposure alters mouse hepatic angiogenic gene expression.
Inhalant nitrites are drugs of abuse that have been shown to enhance tumor growth rate in mice and are epidemiologically linked to an increased risk of Kaposi's sarcoma. Because nitrites produce nitric oxide, we hypothesized that their toxicological effects might be partly mediated via regulation of angiogenic factors such as vascular endothelial growth factor (VEGF). Preliminary studies showed that isobutyl nitrite (ISBN) incubation stimulated VEGF protein expression in J774 macrophage cells. C57BL/6 mice exposed to ISBN in air exhibited significant up-regulation of VEGF protein and mRNA in the liver, but not in the lung. Liver mRNA expression of VEGF receptor 2 (VEGFR-2), VEGFR-3, Smad5, and Smad7 was also significantly altered. These results demonstrate that in vivo exposure to an inhalant nitrite results in altered tissue expression of VEGF and its receptors, suggesting that some of its toxicological effects may be mediated partly through a mechanism involving angiogenesis.
Tran
Doanh C
DC
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
Yeh
Kai-Chuan
KC
Brazeau
Daniel A
DA
Fung
Ho-Leung
HL
D000280:Administration, Inhalation; D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic; D009573:Nitrites / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis / Q000235:genetics
D009573:Nitrites; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; C018086:isobutyl nitrite