Repair of Chemical Damage to Human DNA

Carcinogenesis Program Biology Division Oak Ridge National Laboratory Oak Ridge Tennessee 

---

J. D. Regan and R. B. Setlow, Repair of chemical damage to human DNA, in Chemical Mutagens Principles and Methods for Their Detection, Vol. 3 (A. Hollaender, ed.), pp. 151-170, Plenum Press, New York (1973). 

Rephcation errors, even with a very efficient repair system, lead to the accumulation of mutations. A human has 10 nucleated cells each with 3 X 10 base pairs of DNA. If about 10 cell divisions occur in a lifetime and 10 mutations per base pair per cell generation escape repair, there may evenmaUy be as many as one mutation per 10 bp in the genome. Formnately, most of these will probably occur in DNA that does not encode proteins or will not affect the function of encoded proteins and so are of no consequence. In addition, spontaneous and chemically induced damage to DNA must be repaired. 

Cadmium inhibits plasma membrane calcium channels and Ca -ATPases. It also inhibits repair of DNA damaged by various chemicals, an effect which is believed to be associated with the induction of tumors. Although cadmium forms a metallothionein, the preformed cadmium metallothionein is nephrotoxic (toxic to the kidneys) it is suggested that effects occur when, at some stage in the kidney, the cadmium is dissociated from the metallothionein. In Itai-Itai disease (see Chronic Toxicity, Human section), patients were found to have chromosome abnormalities. 

---