We examined the binding of various steroid hormones to DNA in vitro by means of
32P-postlabeling. Seventeen steroid hormones and cholesterol (CS) were incubated with human liver DNA at 37°C for 1 h ...under aerobic conditions in the absence of catalysis. The reaction mixtures were analyzed by the nuclease P-1 version of
32P-postlabeling. The results showed that cortexolone (CX), prednisolone (PS), cortisone (CN), cortisol (CL), tetrahydrocortisol (TC), corticosterone (CC), 11-deoxycorticosterone (DC), dexamethasone (DX), dihydrocortisol (DL), and aldosterone (AL) covalently bound with DNA. However, progesterone (PG), 17α-hydroxyprogesterone (HG), estrone (E1), estradiol (E2), estriol (E3), testosterone (TS), cortol (CR) and the original compound for biosynthesis, CS, did not form adducts. In absence of DNA, the steroids themselves did not give rise to any spot on TLC under the same conditions. The dose-responses of DNA binding by DC, DL, CC, CL and CN were linear. The relative adduct labeling of reactive steroids at a concentration of 2 mM were as follows: 68.8 (CX), 53.2 (PS), 39.6 (CN), 29.9 (CL), 20.9 (TC), 12.9 (CC), 12.3 (DC), 7.5 (DX), 4.7 (DL), 1.2 (AL) adducts per 10
8 nucleotides. Reactive and nonreactive steroids were distinguishable by the presence or absence of the carbonyl group (-CO-CH
2OH) at carbon seventeen (C
17) of the cholesterol skeleton. This implies that the electrophilic carbonyl or a neighboring group perhaps involved in the formation of covalent bond with DNA. To investigate the nature of target base(s) of these DNA reactive steroids, mononucleotides of all four bases of DNA were reacted with CN, CL, CC and cochromatographed with the obtained spots of DNA reactions. The results of which stated that these steroids and guanine reaction gave the same spots as observed in DNA reaction, indicating guanine is the main target of these DNA reactive steroids. Hep G2 human hepatocellular carcinoma cells were used as an alternative model. Although nine steroids (CL, DL, TC, PS, DX, PG, E2, TS, CR) did not react with intracellular DNA under our experimental conditions, our findings suggested that some hormonal steroids can form covalent DNA adducts in vitro.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We report a case of retroperitoneal cystic mesothelioma. The patient was a 42-year-old woman with no particular problems in her medical history. She first presented to another hospital becouse of ...common cold, where an abnormal mass in her lower abdomen was pointed out. Then she was admitted to the hospital. The findings obtained by Computed tomography, ultrasonography and barium enema showed a large cystic tumor probably originated from the retroperitoneum. Laparotomy was performed. Surgical exploration showed that a solitary cystic mass was located behind the descending colon and compressed the colon imward. The postoperative histological findings revealed that the tumor was cystic mesothelioma. This histological classification can be achieved by histochemical and immunohistochemical studies with keratin, colloid-Fc and CEA. Retroperitoneal cystic mesothelioma is not a common disease, however, it should be taken into consideration in the differential diagnosis of abdominal masses.
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