Dynamics of Bromodeoxyuridine Incorporation into DNA of Squamous Carcinoma Cells During Mid and Late Logarithmic Growth

Abstract

Head and neck squamous carcinoma cell lines, UM-SCC 1, 5, 9, 11B, and 14B, were exposed in vitro to bromodeoxyuridine (BUdR) during logarithmic growth to determine the effects of drug concentration (0.01 to 10 µ M ) and duration of exposure (3, 7, and 10 days) on cell growth and on incorporation of BUdR into DNA. Concentrations of less than 1.0 µ M were not growth inhibitory except with UM-SCC-11B. After 10 days of exposure to 5 µ M BUdR, survival fractions for all lines ranged from 2 to 65% of controls. Replacement of thymidine by BUdR in DNA was assessed by gas chromatography/mass spectroscopy. Percentage replacement (% R) was described by the equation % R = 100 ( C/t ) s /[( C/t ) 50 s + ( C/t ) s ], where C is the concentration of BUdR (µ M) , t is the time in days, s is a constant, and ( C/t ) 50 is a constant corresponding to % R = 50%. BUdR incorporation reached a time-and concentration-dependent maximum that, after 3 to 7 days of culture in 10 µ M BUdR, ranged from 30 to 60% R. Subsequently, % R declined with time even though the cells were fed daily with fresh BUdR-containing medium.