Metallomics of clear cell Renal Cell Carcinoma in long term tobacco smoking patients identifies a different metabolic signature

Abstract

By Dina Secic, Biochemistry; Julio Landero, University of Cincinnati; Maria Czyzyk-Krzeska, University of Cincinnati; James Reigle, University of Cincinnati; Mario Medvedovic, University of Cincinnati; Jarek Meller, University of Cincinnati

Advisor: Julio Landero

Abstract: Cigarette smoking is a known risk factor for kidney cancer, yet the mechanism(s) involved are unknown. Cadmium and arsenic are abundant in Cigarette smoke. Humans, haven't evolved to excrete cadmium, once it enters our system it accumulates in the liver, eventually goes back into circulation, to be finally be permanently retained in the kidneys. On the other hand, arsenic can be excreted in the kidneys after methylation for which S-adenosyl methionine (SAM) is the key methyl group donor, which is shared for DNA methylation. The goal of my part of this project was to determine the role of different toxic metal fractions on the observed different metabolic behaviors between kidney tissues and tumors from non-smokers (NS) versus life-time smokers (LTS). Inductively Coupled Plasma Mass Spectrometry (ICP-MS) coupled to liquid chromatography (HPLC) was used to quantify the different metals species in the samples. It was found that in LTS, there is an increase in arsenic and cadmium levels in kidney followed by a change in speciation. As was found mostly free and inorganic in LTS vs methylated and bound in NS. Cd was distributed across all molecular masses in LTS vs concentrated in storage proteins in NS. A redistribution of copper from buffering proteins to respiratory complexes corresponded to the metabolic changes observed by metabolomics. This never-before reported metabolic behavior calls for a personalized treatment different from the current protocol in smokers.