Capacities of Mouse Embryo Cells for Induction of Unscheduled DNA Synthesis by 4-Nitroquinoline 1-Oxide in Primary Culture Systems2

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Abstract
Because 4-nitroquinoline 1-oxide (4-NQO) selectively induces lung tumors in offspring of ICR/Jcl inbred mice, unscheduled DNA synthesis (UDS) induced by 4-NQO was investigated with use of confluent primary cultures of cells from six different organs of ICR/Jcl mouse embryos. The UDS level of lung-derived cells (lung cells), as measured with hydroxyurearesistant incorporation of [3H]thymidine into cellular DNA in the presence of 4-NQO, was at least threefold lower than levels in cells from skin, intestine, kidney, liver, and brain, when compared at equitoxic doses of 4-NQO or equimolar binding of 4-NQO to DNA. Autoradiographic studies also revealed that the percentage of UDS-positive nuclei in lung cells was about one-fifth of other cell types. Cytotoxic examinations showed that the lung cells were the most sensitive to the lethal action of 4-NQO. These results suggest that the capacity of cells from the target organ to repair 4-NQO damage is intrinsically much lower than the capacity of cells from nontarget organs.