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Scissions of Proteins Linking DNA in Cultured Mammalian Cells Induced by 4-Nitroquinoline 1-Oxide and Their Repair¹

Department of Virology, Institute of Medical Science, University of Tokyo, P. O. Takanawa 108, Tokyo, Japan

The rejoining of double-strand scissions of DNA induced by 4-nitroquinoline 1-oxide (4NQO) was studied in cultured mouse cells, strains FM3A and L·P3. FM3A cells seem to be more sensitive to 4NQO than L·P3 cells; under otherwise similar conditions, 1 x 10^-6 M 4NQO caused a decrease in the sedimentation rate of DNA of FM3A cells comparable with that caused by 1 x 10^-5 M 4NQO in L·P3 cells.

The scissions caused by a low concentration of 4NQO in FM3A were completely rejoined on incubation of cells in medium without 4NQO (recovery incubation). However, with increase in concentration above 3 x 10^-6 M 4NQO the extent of breakage increased, recovery was incomplete, and the fraction which was still unrepaired after recovery incubation increased. Concomitant with repair of DNA the growth capacity of the cells was regained. However, as the unrepaired fraction increased with increase in the concentration of 4NQO, the viability of the cells decreased. Cell killing induced by 4NQO was suggested to be due to disorder of cell functions caused by irreparable double-strand scission of DNA.

With a sucrose gradient containing Pronase, it was found that treatment of the cells with the lower concentrations of 4NQO, i.e., 1 x 10^-5 M for L·P3 cells and 1 x 10^-6 M for FM3A cells, or treatment of control DNA with Pronase alone in the gradient had the same effect in inducing a decrease in the sedimentation rate of DNA as both of these treatments in combination. Treatment of the cells with higher concentration of 4NQO resulted in a greater extent of decrease in the sedimentation rate of DNA than treatment of control DNA with Pronase alone.

¹ This paper is Paper 18 of a series "Carcinogenesis in Tissue Culture," and was supported by a grant from the Japanese Ministry of Education.

Received 6/ 4/71. Accepted 2/11/72.