UNSCHEDULED DNA-SYNTHESIS AND MITOCHONDRIAL-DNA SYNTHETIC RATE FOLLOWING INJURY OF THE FACIAL-NERVE

Unscheduled DNA synthesis (UDS) of nuclear DNA and mitochondrial (mt) DNA synthetic rates were determined autoradiographically in different cell types of the rodent brain 14 days after unilateral facial nerve t ransection. In addition to an increased synthetic rate of mtDNA in fac ial motoneurons 12 h after axotomy, a significant increase of UDS, i.e ., DNA repair, and mtDNA synthesis were found in the regenerating faci al nucleus 4 days after axotomy. Specificity of the observed labeling was confirmed by injection of (H2O)-H-3 instead of [H-3]thymidine. Usi ng electron microscopic autoradiography, it was further shown that cyt oplasmic labeling of neurons was mainly due to incorporation of radioa ctive label into mitochondria, indicating their subsequent multiplicat ion by division. The observation that Northern blot signals for O-6-al kylguanine-DNA-alkyltransferase mRNA from homogenized facial nuclei of both the axotomized and normal side remained unchanged over 14 days a fter axotomy indicated that the observed DNA-repair activity was not c aused by endogenously produced alkylating agents. The combined presenc e of transiently increased UDS, enhanced mtDNA synthesis and elevated protein synthetic rates of regenerating motoneurons (as shown in the l iterature) suggests that free radicals produced by mitochondria in inj ured nerve cells could cause unspecific DNA damage followed by immedia te repair.