In vitro exposure of guinea pig pancreatic slices to 4-hydroxyaminoquinoline 1-oxide (HAQO) resulted in increased [methyl-3H]thymidine ([3H]TdR) incorporation into DNA, both in the presence and absence of hydroxyurea (HU). Normal DNA replicative synthesis, but not DNA repair synthesis, was suppressed by HU. The increase in [3H]TdR incorporation into DNA, in the presence of HU, represented DNA repair synthesis in response to DNA damage induced by HAQO. Exposure of pancreatic slices to 10-6 to 10-5 m concentrations of HAQO did not significantly increase thymidine incorporation; however, a 15-min exposure to 10-4 m HAQO induced a significant increase in HU-insensitive [3H]TdR incorporation into DNA. Kinetics of [3H]TdR incorporation suggests that most of the DNA repair synthesis occurs during the 2 hr following HAQO-induced DNA damage.
Supported by Contract NO1-CP-23284 from the National Cancer Institute, Bethesda, Md.