Human mesothelial cells are unusually susceptible to simian virus 40-mediated transformation and asbestos cocarcinogenicity.
Mesothelioma, a malignancy associated with asbestos, has been recently linked to simian virus 40 (SV40). We found that infection of human mesothelial cells by SV40 is very different from the semipermissive infection thought to be characteristic of human cells. Mesothelial cells are uniformly infected but not lysed by SV40, a mechanism related to p53, and undergo cell transformation at an extremely high rate. Exposure of mesothelial cells to asbestos complemented SV40 mutants in transformation. Our data provide a mechanistic explanation for the ability of SV40 to transform mesothelial cells preferentially and indicate that asbestos and SV40 may be cocarcinogens.
Bocchetta
M
M
Cancer Immunology Program, Department of Pathology, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL 60153, USA.
Di Resta
I
I
Powers
A
A
Fresco
R
R
Tosolini
A
A
Testa
J R
JR
Pass
H I
HI
Rizzo
P
P
Carbone
M
M
D001194:Asbestos / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology* / Q000821:virology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000821:virology; D006801:Humans; D008654:Mesothelioma / Q000209:etiology / Q000473:pathology* / Q000821:virology; D013539:Simian virus 40; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D002273:Carcinogens; D016159:Tumor Suppressor Protein p53; D001194:Asbestos