Establishment of a human in vitro mesothelial cell model system for investigating mechanisms of asbestos-induced mesothelioma.
Normal human mesothelial (NHM) cells were transfected with a plasmid containing SV40 early region DNA. Individual colonies of transformed cells from several donors were subcultured for periods of 5 to 6 months and 60 to 70 population doublings (PDs) before senescence, in contrast to a culture lifespan of approximately 1 month and 15 PDs for NHM cells. One such culture, designated MeT-5A, escaped senescence and has been passaged continuously for more than 2 years. These cells had a single integrated copy of SV40 early region DNA in their genome, expressed SV40 large T antigen, and exhibited features of mesothelial cells including sensitivity to the cytotoxic effects of asbestos fibers. One year after injection subcutaneously or intraperitoneally in athymic nude mice, these cells remain nontumorigenic, and therefore are a potential model system for in vitro fiber carcinogenesis studies.
Ke
Y
Y
Division of Cancer Etiology, National Cancer Institute, Bethesda, Maryland 20892.
Reddel
R R
RR
Gerwin
B I
BI
Reddel
H K
HK
Somers
A N
AN
McMenamin
M G
MG
LaVeck
M A
MA
Stahel
R A
RA
Lechner
J F
JF
Harris
C C
CC
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000032:analysis; D001194:Asbestos / Q000009:adverse effects* / Q000494:pharmacology; D017639:Asbestos, Amosite; D015197:Carcinogenicity Tests; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D006023:Glycoproteins / Q000235:genetics; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007621:Karyotyping; D008654:Mesothelioma / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D010957:Plasmids; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors; D015849:Plasminogen Inactivators; D010997:Pleural Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D013539:Simian virus 40 / Q000276:immunology / Q000502:physiology; D014162:Transfection
D000952:Antigens, Polyomavirus Transforming; D006023:Glycoproteins; D006133:Growth Substances; D015849:Plasminogen Inactivators; D012333:RNA, Messenger; D017639:Asbestos, Amosite; D001194:Asbestos; D010960:Plasminogen Activators