Oropharyngeal aspiration of particulate hexavalent chromium increases chromium levels in lung and liver, and induces essential metal dyshomeostasis in lung, liver, and blood

Abstract

Background

Hexavalent chromium [Cr(VI)] is a known human lung carcinogen with widespread exposure risks, yet how it causes cancer is still unclear. Cr(VI) causes dyshomeostasis of essential metals in the brains of exposed rats and is considered a biomarker of lung cancer, yet whether Cr(VI) causes metal dyshomeostasis in the lung is unknown. Cr(VI) particles impact at lung bifurcations causing tumors at these sites, indicating the bronchial branching is a key consideration for its toxicity. This study chose guinea pigs because, like humans, they have a dichotomous bronchiole branching pattern. The aim of this study was to investigate Cr accumulation and essential metal dyshomeotasis in the lung, liver and blood.

Methods

We acutely and subchronically exposed guinea pigs to zinc chromate through oropharyngeal aspiration. We collected lung, liver and blood, and quantified metal levels using inductively coupled plasma-mass spectrometry.

Results

Our data indicate oropharyngeal Cr(VI) exposure results in Cr accumulation in the lung and liver. We also measured zinc levels, and despite using zinc chromate as our representative Cr(VI) compound we observed no changes. This study is the first study to consider Cr(VI)-induced essential metal dyshomeostasis in the lung, liver and blood, and we found Cr(VI) exposure changed the levels of essential metals like potassium, sodium, calcium, magnesium, iron, copper, cobalt, manganese, selenium and molybdenum.

Conclusions

This study established a new relevant model to study Cr(VI)-carcinogenesis and our results suggest metal dyshomeostasis could be part of the Cr(VI) carcinogenic mechanism and these effects should be considered in future mechanistic studies.