Autor: |
Mangold, K.A., Hubchak, S., Mangino, M.M., Laconi, S., Scarpelli, D.G. |
Zdroj: |
Carcinogenesis; 1994, Vol. 15 Issue 9, p1979-1984, 6p |
Abstrakt: |
Neoplastic transformation of Syrian golden hamster (SGH) pancreatic duct cells was induced by treatment with the direct-acting carcinogens -methylnitrosourea (MNU) and -(2-hydroxypropyl)nitrosourea (HPNU), with subsequent selection by sustained culture in serum- and epidermal growth factor (EGF)-deprived medium. The present study examines the efficacy of serum and EGF deprivation as a selection pressure and the effect of the carcinogen dose, frequency and interval of exposure on tumorigenesis and K- mutation. Selection of carcinogen-initiated duct cells by serum and EGF deprivation is highly reproducible and effective, increasing the incidence of tumors from 26 to 93% for MNU or from 0 to 100% for HPNU. SGH pancreatic duct cells exposed to 0.5 mM MNU for 13 weeks (long-treatment schedule) produced K- mutations at codon 12 in six of six tumors. However, when cells were exposed to 0.125, 0.25 or 0.5 mM MNU daily for 5 days (short-treatment schedule), mutations of K- at codon 13 were identified in four of 16 tumors, the remaining 12 showing no mutations. Duct cells exposed to 0.5 mM HPNU by the short-treatment schedule produced K- mutations in codon 13 in six of six tumors, as contrasted to 12 tumors that developed from cells exposed to 0.125 or 0.25 mM HPNU, which all contained K- codon 12 mutations. The current experiments demonstrate that K- mutation in pancreatic carcinogenesis by MNU or HPNU can be modified by the nature and dose of the carcinogen as well as the frequency and duration of exposure. [ABSTRACT FROM PUBLISHER] |
Databáze: |
Complementary Index |
Externí odkaz: |
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