Effect of carcinogen dose on the dynamics of neoplastic development in rat tracheal epithelium

Journal Article · Sun Oct 31 23:00:00 EST 1982 · Cancer Res.; (United States)

OSTI ID:5774445

Terzaghi, M ^[1]; Nettesheim, P; Riester, L

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1. Oak Ridge National Lab., TN

The aim was to analyze carcinogen dose effects on the development of carcinogen-altered preneoplastic epithelial cell populations following exposure to 7,12-dimethylbenz(a)anthracene (DMBA). Upon exposure to carcinogen, cells appear in the tracheal epithelium which are distinguishable by an enhanced in vitro growth capacity. Cultures established from carcinogen-exposed cells form expanding epithelial foci (EF). Designated EF-forming units (EFFU), these clonogenic units often escape senescence permanently and may become neoplastic after repeated subculturing. Clonogenic units give rise to subculturable progeny (EFFU/sub s/) and to progeny which became anchorage independent (EFFU/sub s,ag/sup +//). In the tracheal cell culture system, anchorage-independent growth is highly correlated with oncogenicity in vivo. Tracheas were exposed in vivo for 4 weeks to DMBA in doses ranging from 5 to 335 ..mu..g. Exposure to DMBA resulted in a 100- to 500-fold increase in frequency of EFFU, but no definitive carcinogen dose-response effect was detected on the number of clonogenic cells forming EF or subculturable EF, although there was some indication that the latter might be increasing with increasing dose. There was a marked carcinogen dose effect on the frequency and rate of appearance of EFFU/sub s,ag/sup +//. The data suggest that the carcinogen dose affects either the rate of growth of EFFU/sub x,ag/sup +//, the cell compartment with neoplastic potential, or the conversion rate of EFFU/sub s/ to EFFU/sub s,ag/sup +//.

• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 5774445
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 42; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
AROMATICS
CARCINOGENESIS
CELL CULTURES
COLONY FORMATION
CONDENSED AROMATICS
DATA
DIMETHYLBENZANTHRACENE
EXPERIMENTAL DATA
INFORMATION
MAMMALS
NUMERICAL DATA
ONCOGENIC TRANSFORMATIONS
ORGANIC COMPOUNDS
PATHOGENESIS
RATS
RESPIRATORY SYSTEM
RESPIRATORY TRACT CELLS
RODENTS
TRACHEA
VERTEBRATES