RESPONSE re: markers of DNA repair and susceptibility to cancer in humans: an epidemiologic review

Berwick and Vineis (1) recently summarized results from human studies on DNA repair and cancer susceptibility markers. They carefully discussed the aspects relating to technical validity, such as reproducibility, sample size, and selection of control subjects. However, the primary question about the biologic relevance of the assay systems used was discussed in only a few sentences. Of the 64 tabulated studies, three reported DNA polymorphisms, two reported cultured fibroblast assays, two reported kinetics from skin biopsies in situ, and the remaining 57 were different types of lymphocyte assays. The lymphocyte assays have been carried out to make inferences about DNA repair functions in other organs in situ. Circulating lymphocytes are dormant cells and any functional tests on them require extensive in vitro manipulation. The relevance of the tests remains to be established, in spite of the large number of times that they have been used. A relevant repair test measures removal of specific DNA damage in the target organ, when it has been demonstrated that DNA repair is the only means of damage removal (i.e., the adduct is chemically stable and no appreciable cell death and replication takes place). The two cited studies using kinetic tests on skin biopsies do fulfill the criterion of biologic relevance. Recently, a repair test was developed by measuring the removal of specific UV radiation (UVR)-induced DNA damage in human skin in situ (2). The method was based on the 3 2 P-