Free Radicals and Breast Cancer
For the most part, the article in the Forum section titled "Free Radicals and Breast Cancer" [ EHP 104:821 (1996)] accurately describes our paper "Progression of Human Breast Cancers to the Metastatic State Is Linked to Hydroxyl Radical-induced DNA Damage" ( 1 ). However, it was claimed that
Some scientists have questioned the methodologies used by Malins and note that studies published in the February 1996 issue of Carcinogenesis and the December 1995 issue of Chemical Research in Toxicology failed to duplicate Malins' initial results using identical methods.
The authors of the articles, Douki et al. ( 2 ) and Ravanat et al. ( 3 ), were concerned primarily with the possibility of DNA base oxidations in the formation of trimethysilyl derivatives for gas chromatography-mass spectrometry (GC-MS). The focus was not on our work and the authors did not attempt to duplicate our results or dispute our conclusions. In our studies of base changes in relation to breast cancer, we consistently compared control and test samples under identical conditions that favored the exclusion of oxygen. Ravanat et al. ( 3 ) found no fault with this approach, stating that
the differences in the levels of 8-oxoGua observed between controls and treated samples should not be due to the artifactual oxidation of guanine during the derivatization, assuming that the samples were treated in an identical fashion.
This conclusion would logically include other bases, although guanine may be particularly susceptible to oxidation.
The Forum article does not mention the findings of Musarrat et al. ( 4 ) or Nagashima et al. ( 5 ), which are consistent with our conclusions linking base damage to breast cancer ( 6 ). Overall, we applaud the effort to explore the possibility that individual bases are artifactually oxidized using the GC-MS procedures, particularly because of mounting evidence relating the base lesions to carcinogenesis. For our part, we have recently employed 13C/15N-labeled bases as standards to correct for possible oxidation in determining individual base lesions.
Donald C. Malins
Pacific Northwest Research Foundation
Seattle Washington
References
1. Malins DC, Polissar NL, Gunselman SJ. Proc Natl Acad Sci USA 93:2557-2563 (1996).
2. Douki T, Delatour T, Bianchini F, Cadet J. Carcinogenesis 17:347-353 (1996).
3. Ravanat JL, Turesky RJ, Gremaud E, Trudel LJ, Stadler RH. Chem Res Toxicol 8:1039-1045 (1995).
4. Musarrat J, Arezina-Wilson J, Wani AA. Prognostic and aetiological relevance of 8-hydroxyguanosine in human breast carcinogenesis. Eur J Cancer 32A:1209-1214 (1996).
5. Nagashima M, Tsuda H, Takenoshita S, Nagamachi Y, Hirohashi S, Yokata J, Kasai H. 8-Hydroxydeoxygranosine levels in DNA of human breast cancers are not significantly different from those of non-cancerous breast tissues by the HPLC-ECD method. Cancer Lett 90:157-162 (1995).
6. Malins DC, Holmes EH, Gunselman SJ. Commentary. Cancer Lett 94:233 (1995).
Editors' note: In view of the implied criticism, the news article refered to by Dr. Malins should have included complete references, identifying authors, articles, and journals. Our apologies to Dr. Malins.
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