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The effects of iqmik derived metals on ROS generation and cytokine response in human gingival epithelial cells

Status Complete
Seeking Researchers No
Start Date 09/01/2011
End Date 09/01/2011
Funding Source Discovery Grant
Funding Amount
Community Partner
Related Course
Last Updated 03/24/2012 11:58PM
Keywords iqmik


  Cindy Knall

Student Researchers
  Gaelen Dwyer


Head and neck squamous cell carcinoma is the sixth most common cancer in the
world and it is especially prevalent in Alaska (St. John et al., 2004). Cancer is the leading cause of death for Alaska Natives, with lung cancer as the most prevalent form (Renfler et al.,2005). Smokeless tobacco is used by Alaska Natives with nearly eight times the frequency of the general population of the United States, and is especially prcvalcnt among thc Alaska Natives particularly in the Yukon-Kuskokwin Delta. An indigenous application of smokeless tobacco, iqmik, is the most common thrm n this region. The elders from the Yukon Kuskokwin Delta were questioned and they estimated that 50% to 80% of the population used iqmik. It is shared with elders and children as young as 5 years old and has been in use for over 150 years (Blanchette et al., 2002).

Iqmik is a combination of tobacco leaves mixed with Phellinus igniarius (punk
fungus) or Salix alaxensis (willow) in the absence of punk fungus. The fungus is burned and the ash is mixed with the tobacco by mastication. Historically, the preparer is recorded to be a woman; more recently, public health initiatives have encouraged mixing the fungus and ash without mastication (Blanchette, 2001).

The first objective is to determine the concentrations of three toxic metals, cadmium, nickel and cobalt, in artificial saliva extract from iqmik and determine if the metals are being absorbed into oral epithelial cells. These three metals have been classified as carcinogens by the IARC and they are found in higher concentrations in iqmik than in commercial brands of
smokeless tobacco because they are found in high quantities in the ash that is part of the
iqmik mixture (Pappas et al., 2008). Working hypothesis: The metals, cadmium, cobalt and
nickel from iqmik will be absorbed into the oral epithelial cells.

The second objective is to identify the proinflammatory cellular response to doses of
cadmium, cobalt and nickel comparable to levels identified in iqmik. Cadmium, nickel and
cobalt have been shown to increase ROS generation which can lead to the activation of two
proinflammatory cytokines. IL-6 and IL-8. IL-6 and IL-8 are used as biomarkers for oral squamous cell carcinoma. Working hypothesis: A significant percent of iqmik-induced ROS. IL-6 and IL-8 response will be directly attributed to the carcinogenic metal component.

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