Erionite and asbestos differently cause transformation of human mesothelial cells.
Malignant mesothelioma (MM) is an aggressive tumor associated with environmental or occupational exposure to asbestos fibers. Erionite is a fibrous zeolite, morphologically similar to asbestos and it is assumed to be even more carcinogenic. Onset and progression of MM has been suggested as the result of the cooperation between asbestos and other cofactors, such as SV40 virus infection. Nevertheless, several cases of MM were associated with environmental exposure to erionite in Turkey, where SV40 was never isolated in MM specimens. We show here that erionite is poorly cytotoxic, induces proliferating signals and high growth rate in human mesothelial cells (HMC). Long term exposure to erionite, but not to asbestos fibers, transforms HMC in vitro, regardless of the presence of SV40 sequences, leading to foci formation in cultured monolayers. Cells derived from foci display constitutive activation of Akt, NF-kappaB and Erk1/2, show prolonged survival and a deregulated cell cycle, involving cyclin D1 and E overexpression. Our results reveal that erionite is able per se to turn HMC into transformed highly proliferating cells and disclose the carcinogenic properties of erionite, prompting for a careful evaluation of environmental exposure to these fibers. The genetic predisposition to the effect of erionite is a separate subject for investigation.
Bertino
P
P
Department of DISCAFF and DFB Center, University of Piemonte Orientale A. Avogadro, Novara, Italy.
Marconi
A
A
Palumbo
L
L
Bruni
B M
BM
Barbone
D
D
Germano
S
S
Dogan
A U
AU
Tassi
G F
GF
Porta
C
C
Mutti
L
L
Gaudino
G
G
D001194:Asbestos / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D002478:Cells, Cultured; D003603:Cytotoxins / Q000633:toxicity; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D004848:Epithelium / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D008855:Microscopy, Electron, Scanning; D013997:Time Factors; D017641:Zeolites / Q000633:toxicity*
D003603:Cytotoxins; C083174:erionite; D017641:Zeolites; D001194:Asbestos; D004247:DNA