NAFTA prompts health concerns across the borders.
نویسنده
چکیده
Sublines from the small cell lung cancer (SCLC) cell lines U1285 and U1690, denoted U1285-100, U1285-250, U1690-40 and U1690-150, were adapted to grow in the continuous presence of 100, 250, 40 and 150 ng ml-' doxorubicin (Dox), respectively. The Dox resistance was accompanied by cross-resistance to vincristine (Vcr), Vp-16 and for U1285-100 also to cisplatinum. Sublines of U1690-40 and U1285-100, cultured in absence of Dox for 4 months were only partially reversed with respect to Dox resistance. Neither the parental nor the most Dox resistance sublines had detectable levels of mdr RNA but a small fraction of cells in all cell lines stained weakly positive for P-glycoprotein (P-gp). Verapamil (Ver) at 5 gsM reversed the Dox resistance completely and partly in the U1690 and U1285 sublines, respectively, but did not increase the cellular accumulation of Dox. The cytoplasmic free Ca2" concentration (Ca2+i) was close to 100 nm in both parental cell lines but elevated in the U1285-100 and U1690-40 sublines by 21 and 44%, respectively, and in U1285-250 and U1690-150 by 51 and 91%, respectively. The partly reverted sublines still showed significant but smaller elevations in Ca2+i of 10-30%. Ver was without acute or long term effects of Ca2+i in the U1285-100 and U1690-40 sublines. Selection for Dox resistance in SCLC may thus result in atypical multidrug-resistance characterised by absence of P-gp overexpression and atypical cross-resistance. Although Ver did not seem to affect Dox accumulation it may still work as a resistance modulator. There may be a role for increased Ca2+i in drug resistance in SCLC cells, but resistance reversal by Ver seems unrelated also to changes in Ca2+i.
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عنوان ژورنال:
- Environmental Health Perspectives
دوره 101 شماره
صفحات -
تاریخ انتشار 1993