Formation of 8‐hydroxy‐2′‐deoxyguanosine and 4‐hydroxy‐2‐nonenal‐modified proteins in human renal‐cell carcinoma

International Journal of Cancer - Tập 58 Số 6 - Trang 825-829 - 1994
Keigo Okamoto1,2, Shinya Toyokuni1, Kôji Uchida3, Osamu Ogawa2, Jun Takenewa2, Y Kakehi2, Hidefumi Kinoshita2, Y Hattori-Nakakuki1, Hiroshi Hiai1, Osamu Yoshida2
1Departments of Pathohgy, Faculty of Medicine, Kyoto University, Kyoto
2Departments of Urology, Faculty of Medicine, Kyoto University, Kyoto
3Laboratory of Food and Biodynamics, Nagoya University School of Agriculture, Nagoya 464-01, Japan

Tóm tắt

AbstractTo study the possible involvement of reactive oxygen species (ROS) in the tumor biology of human renal‐cell carcinoma (RCC), we analvzed 35 cases of RCC for 2 parameters of oxidative damage: 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), a mutation‐prone DNA‐ base ‐modified product, was measured by means of high‐performance liquid chromatography (HPLC) with an electrochemical (EC) detector, and 4‐hydroxy‐2‐nonenal (HNE)‐modified proteins were measured with a poly‐clonal antibody against HNE‐modified proteins. A 54% higher content of 8‐OHdG was found in RCC than in the corresponding non‐tumorous kidney, suggesting that the DNA of RCC is more exposed to ROS than is the DNA of non‐tumorous kidneys. Immunohistochemistry for HNE‐modified proteins showed a distinct staining pattern of fine to coarse granularity in the cytoplasm of RCC (n = 15), implying that lipid peroxidation products are located in cytoplasmic organelles. These results suggest that RCC constitutionally elaborates more ROS than is produced by the non‐tumorous parts of kidneys. No correlation was found between clinical stage, histology, age or sex and the 2 parameters examined.

Từ khóa


Tài liệu tham khảo

Bennington J. L., 1975, Atlas of tumor pathology. Tumors of the kidney, renal pelvis, and ureter, 93

Cerutti P. A., 1985, Pro‐oxidant states and tumor promotion, Science (Wash.), 227, 375, 10.1126/science.2981433

Cheno K. C., 1992, 8‐hydroxyguanine, an abundant form of oxidative DNA damage, causes G → T and A → C substitutions, J. biol. Cham., 267, 166, 10.1016/S0021-9258(18)48474-8

10.1016/0891-5849(91)90192-6

10.3109/10715769209049161

Halliwell B., 1989, Free radicals in biology and medicine, 1

10.1016/0092-8674(89)90833-7

Luna L. G., 1968, Manual of histologic staining methods of the Armed Forces Institute of Pathology, 5

Malins D. C., 1991, Major alteration in the nucieotide structure of DNA in cancer of the female breast, Cancer Res., 51, 54311

10.1002/1097-0142(19930515)71:10<3036::AID-CNCR2820711025>3.0.CO;2-P

10.1016/0006-291X(92)90218-A

Mostofi F. K., 1981, International histological classification of tumors

10.1084/jem.153.4.766

10.1016/0014-5793(79)80049-6

Ogawa O., 1991, Alleic loss at chromosome 3p characterizes clear‐cell phenotypes of renal‐cell carcinoma, Cancer Res., 51, 949

10.1016/0014-5793(92)81093-2

10.1093/carcin/10.5.827

10.1002/1097-0142(19930801)72:3<783::AID-CNCR2820720325>3.0.CO;2-U

10.1002/j.1460-2075.1991.tb07761.x

Stenzl A., 1989, The natural history of renal‐cell carcinoma, Semin. Urol., 7, 144

Szatrowski T. P., 1991, Producrion of large amount of hydrogen peroxide by human tumor cells, Cancer Res., 51, 794

10.1093/jnci/83.22.1668

10.1073/pnas.91.7.2616

10.1073/pnas.90.18.8742

Wheeler R. H., 1979, Effect of hyperbaric oxygen on the cytotoxicity of adriamycin and nitrogen mustard in cultured Burkitt's lymphoma cells, Cancer Res., 39, 370

10.1021/bi00482a011

Yogoda A., 1989, Chemotherapy of renal‐cell carcinoma: 1983‐1989, Semin. Urol., 7, 199

Thông tin
Thông tin xuất bản

International Journal of Cancer

Tập 58 Số 6

825-829

Thông tin tác giả