T.M. Wardell, E. Ferguson, P.F. Chinnery, N. Howell, G. Jackson, A. Craft, R.N. Lightowlers, D.M.Turnbull. Department of Neurology, Medical School, Newcastle upon Tyne. MtDNA is susceptible to mutation due to the availability of only limited repair mechanisms. In addition to this a lack of protective proteins results in liability to damage from other agents. The effects of chemotherapeutic drugs and radiotherapy used in the treatment of cancer upon mtDNA integrity was investigated.
Radiation can induce altered bases and both single and double strand breaks.
It has been reported that X-irradiation induces mtDNA deletions in cultured cells. Chemotherapeutic drugs such as alkylating agents may cause bulky adducts, or block base synthesis, for example methotrexate, which may be compared with the recent observation that multiple mtDNA deletions are caused by a defect in thymidine phosphatase. If mtDNA is mutated by such therapy, then accumulation of mtDNA mutations could lead to some of the adverse effects of treatment. In addition, if mtDNA was shown to be particularly sensitive to such therapy then it could provide a valuable genetic dosimeter to be monitored in patients. Two studies were performed as part of this investigation.