Derivation of tumorigenic and non-tumorigenic mouse alveolar type-II cell lines from fetal type-II cells after a combined in vivo/in vitro carcinogen treatment.
Alveolar type-II cells were isolated from the lungs of fetuses (day 18 of gestation) of the A/WySnAf (A/Sn) mouse strain, which were treated in utero at day 15 with the directly-acting carcinogen N-ethyl-N-nitrosourea (ENU). The isolated type-II cells were again treated with ENU during their initial growth in vitro. After a prolonged culture period, 5 cell lines were obtained, which were identified as type-II cell lines. Differences between cell lines were found with respect to contact-inhibited growth, cell doubling time and ability to grow in a serum-free medium. Two out of the 5 cell lines produced highly invasive type-II cell carcinomas after s.c. injection of 5 x 10(6) cells into nude mice. Thus, both tumorigenic and non-tumorigenic mouse alveolar type-II cell lines were derived after this combined in vivo and in vitro carcinogen treatment of fetal mouse alveolar type-II cells. This offers the possibility of studying in vitro the factors thought to influence lung tumorigenesis in vivo. In addition, our findings strongly suggest that alveolar type-II cells are the progenitor cells of malignant mouse lung tumors.
Oomen
L C
LC
Division of Molecular Genetics, Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Amsterdam.
Calafat
J
J
Ten Have-Opbroek
A A
AA
Egberts
J
J
Demant
P
P
D000818:Animals; D002455:Cell Division; D003470:Culture Media; D005038:Ethylnitrosourea; D005260:Female; D005333:Fetus; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010743:Phospholipids / Q000737:chemistry; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000473:pathology; D014407:Tumor Cells, Cultured
D003470:Culture Media; D010743:Phospholipids; D005038:Ethylnitrosourea