Cholesterol oxides and carcinogenesis
Tóm tắt
Experimental evidence indicates a relationship between cholesterol α‐epoxide and skin cancer, and exposure of skin fibroblasts to ultraviolet radiation enduces formation of significant levels of this oxide. Colon cancer is also etiologically linked to cholesterol oxidation products. Higher than normal levels of cholestanetriol have been found in patients with colon cancer and also in those with precancerous disorders such as adenomatous polyps and ulcerative colitis. Higher than normal levels of cholesterol α‐epoxide have been found in breast fluid aspirates of women with benign breast disease, with or without atypical hyperplasia of the epithelium, and this may be a factor in the increased incidence of breast cancer associated with hyperplasia. Similarly, the observed increased levels of cholesterol α and β‐epoxides in prostatic fluid of men with benign prostatic hypertrophy may be associated with subsequent development of prostate cancer.
Cholesterol α‐epoxide has been found to be mutagenic to fibroblasts in culture and to induce morphological transformation in hamster embryo cells and in mouse C3H cells. 25‐Hydroxycholesterol and 20α‐hydroxycholesterol are potent suppressors of generation and proliferation of tumor‐specific cytotoxic T lymphocytes.
Although investigations into the role of cholesterol oxidation products in cancer are still in the early stages, evidence to date indicates a potentially significant role in the induction of some types of cancer.
Từ khóa
Tài liệu tham khảo
Bischoff F, 1946, The production of a carcinogenic agent in the degration of cholesterol to progesterone, Cancer Res, 6, 403
Bischoff F, 1957, Cocarcinogenic activity of cholesterol oxidation products and sesame oil, JNCI, 19, 977
Koch R, 1964, Moglichkeiten des Eingreifens sensibilisierender und desensibilisierender zusate in der strahlenchemie und‐biologie, Strahlentherapie, 124, 626
Bryson G, 1964, Triolein as a cocarinogen, Fed Proc, 23, 106
Black HS, 1972, A model system for the evaluation of the role of cholesterol α‐oxide in ultraviolet carcinogenesis, Cancer Res, 32, 2630
Black HS, 1973, Formation of a carcinogen of natural origin in the etiology of ultraviolet light‐induced carcinogenesis, Cancer Res, 33, 2094
Wynder EL, 1975, The epidemiology of large bowel cancer, Cancer Res, 35, 3388
Reddy S, 1977, Fecal bile acids and cholesterol metabolites of patients with ulcerative colitis, a high‐risk group for development of colon cancer, Cancer Res, 37, 1697
Reddy S, 1979, Effect of cholesterol metabolites and promoting effect of lithocholic acid in colon carcinogenesis in germ‐free and conventional F344 Rats, Cancer Res, 39, 1521
Hiatt RA, 1982, Breast cancer and serum cholesterol, JNCI, 68, 885
Gruenke LD, 1987, Breast fluid cholesterol and cholesterol epoxides: Relationship to breast cancer risk factors and other characteristics, Cancer Res, 47, 5483
Petrakis N, 1981, Cholesterol and cholesterol epoxides in nipple aspirates of human breast fluid, Cancer Res, 41, 2563
Wrensch MR, 1989, Breast fluid cholesterol and cholesterol β‐epoxide concentrations in women with benign breast disease, Cancer Res, 49, 2168
Swyer GIM, 1942, The cholesterol content of normal and enlarged prostate, Cancer Res, 2, 372
BlackkburnGM RashidA ThompsonMHInteraction of 5 α 6β‐cholesterol oxide with DNA and other nucleophiles.J Chem Soc Chem Commun.:420–421 1979.
Petrakis NL, 1982, Mutagens in nipple aspirates of breast fluid, Banbury Rep, 17, 67
Ts'o POP, 1977, The Molecular Biology of the Mammalian Genetic Apparatus, 241
Humphries GMK, 1979, Potent immunosuppression by oxidized cholesterol, J Immunol, 122, 121, 10.4049/jimmunol.122.1.121
Curtiss LK, 1980, Differences in the characteristics of inhibition of lymphocyte stimulation by 25‐hydroxycholesterol and by the immunoregulatory serum lipoprotein LDL‐In, J Immunol, 125, 1470, 10.4049/jimmunol.125.4.1470
Larsson O, 1986, Kinetics of G1 progression in 3T6 and SV‐3T3 cells following treatment by 25‐hydroxcholesterol, Cancer Res, 46, 1233
Hesketh TR, 1983, Free cytosplasmic calcium concentration and the mitogenic stimulation of lymphocytes, J Biol Chem, 253, 4876, 10.1016/S0021-9258(18)32508-0