Toxicity of Organic and Inorganic Nickel in Pancreatic Cell Cultures: Comparison to Cadmium

Abstract

Nickel compounds are Group 1 carcinogens and possibly cancer-causing in the pancreas. We examined the toxicity of nickel in both 2-D and 3-D pancreatic cell cultures, to determine the LD50 for organic and inorganic nickel in normal and cancerous cells. Assays with cadmium chloride were performed to be a comparison to potential nickel-induced toxicity. Cells were exposed to twelve concentrations of NiCl2 or Ni-(Ac)2 for 48h (2-D), or six concentrations for 48 hours (3-D). There was a significant (P=0.0016) difference between HPNE and AsPC-1 LD50values after cadmium exposure, at 69.9 μM and 29.2 μM, respectively. Neither form of nickel exhibited toxicity in 2-D or 3-D cultures, but after 48h, changes in spheroid morphology were observed. The inability of Ni to reduce viable cell numbers suggests a toxic mechanism that differs from cadmium, also a Group 1 carcinogen. The cell microenvironment was not a factor in nickel toxicity with no changes in viable cells in either 2-D or 3-D cultures. These studies only examined cytotoxicity, and not genotoxicity, a potential mechanism of nickel carcinogenicity. Alterations in DNA function or the expression of apoptotic proteins/processes would take longer to manifest. Current work focuses on cellular changes following extended nickel exposure.

Uloga nikla, toksičnog metala, u nastanku karcinoma pankreasa još uvek nije u potpunosti ispitana. Cilj rada je da ispita toksičnost nikla (Ni) u 2-D i 3-D kulturi ćelija pankreasa, kako bi se utvrdila LD50 vrednost za organski i neorganski nikl u normalnim i tumorskim ćelijama. Ispitivanja su izvršena i sa kadmijumom (Cd), metalom čija je uloga u nastanku karcinoma pankreasa potvrđena u prethodnim istraživanjima, a u svrhu poređenja sa potencijalnom toksičnošću izazvanom Ni. Ćelije su bile tretirane sa 12 različitih koncentracija NiCl2 ili Ni-(Ac)2 tokom 48h (2-D), odnosno sa šest različitih koncentracija tokom 48 sati (3-D). Nijedan oblik Ni nije ispoljio toksičnost u 2-D ili 3-D kulturama, ali nakon 48h primećene su promene u sferoidnoj morfologiji. Nemogućnost Ni da smanji broj vijabilnih ćelija sugeriše mehanizam karcinogeneze različit od mehanizma koji ispoljava Cd. Ipak, da bi se uočile izmene u funkciji DNK ili izražavanju apoptotičkih proteina/procesa potrebno je duže vremena, pa su dalja istraživanja upravo fokusirana na ćelijske promene nakon produžene izloženosti nikla.