8-oxo-7,8-dihydroguanine level - the DNA oxidative stress marker - recognized by fluorescence image analysis in sporadic uterine adenocarcinomas in women.

OBJECTIVES: In the case of carcinogenesis in human endometrium no information exists on tissue concentration of 8-oxo-7,8-dihydroguanine, the DNA oxidative stress marker This was the main reason to undertake the investigation of this DNA modification in human uterine estrogen-dependent tissue cancers. MATERIAL AND METHODS: In order to estimate the level of oxidative damage, 8-oxo-7,8-dihydroguanine was determined directly in cells of tissue microscope slides using OxyDNA Assay Kit, Fluorometric. Cells were investigated under confocal microscope. Images of individual cells were captured by computer-interfaced digital photography and analyzed for fluorescence intensities (continuous inverted 8-bit gray-scale = 0 [black]-255 [white]). Fluorescence scores were calculated for each of 13 normal endometrial samples and 31 uterine adenocarcinoma specimens. Finally the level of the oxidative stress marker was also analyzed according to histological and clinical features of the neoplasms. RESULTS: The obtained data revealed that: 8-oxo-7,8-dihydroguanine levels were higher in uterine adenocarcinomas than in normal endometrial samples (48,32 vs. 38,64; p<0,001); in contrast to normal endometrium there was no correlation between age and DNA oxidative modification content in uterine cancer; highest mean fluorescence intensity was recognized in G2 endometrial adenocarcinomas; level of 8-oxo-7,8-dihydroguanine does not depend on Body Mass Index (BMI) and cancer uterine wall infiltration or tumor FIGO stage. CONCLUSIONS: Our study indicates that accumulation of the oxidized DNA base may contribute to the development of endometrial neoplasia, however oxidative DNA damage does not seem to increase with tumor progression.

[Apurinic/apyrimidinic sites (AP)--stress oxidative marker--in normal and neoplastic human endometrium]. / Liczba miejsc apurynowych/apirymidynowych (AP)--markera stresu oksydacyjnego--w prawidlowym i nowotworowo zmienionym endometrium u kobiet.

OBJECTIVES: To evaluate apurinic/apyrimidinic sites (AP), one of the oxidative stress markers in normal and cancerous human endometrium and determine whether AP sites could be a molecular marker of endometrial cancer advancement. MATERIAL AND METHODS: AP sites were investigated in DNAs of 33 endometrial cancer (EC) and 20 noncancerous endometrial samples using Oxidative DNA Damage Kit Quantitative (Kamiya Biomedical Company). RESULTS: Mean AP sites in noncancerous endometrium was 6.0 +/- 1.21 per 105 base pair. In EC group the mean AP sites level was greater than estimated in the reference group containing proliferative, secretory and hyperplastic endometrial samples (p < 0.05). There was no relation between AP sites and EC FIGO grading or the depth of the uterine wall neoplastic invasion. CONCLUSIONS: In EC mean AP sites level is greater than estimated in noncancerous endometrium. AP sites are not a molecular marker of EC advancement.

Allelic loss at TP53 in metastatic human endometrial carcinomas.

Loss of heterozygosity (LOH) is implicated in the initiation and progression of various human neoplasia, and is observed in both early or in advanced-stage human cancers. The current study was aimed at investigating the frequency of LOH TP53 in human endometrial carcinoma (EC) metastases. LOH was analyzed using 3 intragenic polymorphisms in 38 primary ECs and corresponding metastatic lesions. Allelic loss at intron 1 was detected in 14 out of 38 (37%) primary carcinomas and in 11 out of 38 (29%) metastatic lesions. LOH at intron 1 in primary and metastatic tumors was concomitantly noted in 8 out of 38 (21%) cases. LOH at intron 4 was seen in 46% (17 out of 37) primary ECs and in 35% (13 out of 37) metastatic lesions. LOH at intron 4 in primary tumor/metastasis was concomitantly demonstrated in 27% (10 out of 33) cases. Allelic loss at exon 4 was detected in 5 out of 33 (15%) primary ECs and in one out of 33 (3%) corresponding metastases. Coexistence of LOH TP53 in primary ECs with metastases at intron 1 and intron 4 was observed in three out of 33 (9%) cases. Correlation between allelic loss at intron 1 in primary ECs and corresponding metastases was found (R = 0.475, p = 0.003). Moreover, there was correlation between LOH at intron 1 in metastastic ECs and allelic imbalance at intron 4 in primary uterine tumors (R = 0.416, p = 0.01). There was a relationship between LOH at intron 4 in primary ECs and corresponding metastatic lesions (R = 0.457, p = 0.004). LOH TP53 at intron 4 correlated with the presence of the neoplasm in the uterine cervix (R = 0.319, p = 0.049), and with the non-endometrioid type of primary tumor (R = 0.371, p = 0.024). There was a significant correlation between exon 4 LOH and patient age (less or equal to 50 years and above this age; R = -0.375, p = 0.032). p53 overexpression was present in thirteen out of 38 (34%) cases, both in primary ECs and in metastatic lesions. Overexpression of p53 was higher in non-endometrioid ECs (three out of 5; 60%) than in endometrioid-type uterine tumors (ten out of 33; 30.3%; p = 0.315). p53 overexpression correlated with the presence of cancer in the lumen of fallopian tube(s) (R = 0.032, p = 0.046), and with allelic loss at intron 1 in primary ECs (R = 0.599, p = 0.0001). In conclusion, LOH occurs not only in primary uterine tumors but also in corresponding metastases, with the higher incidence being reported at intron 4 of the TP53. A significant link existed between LOH TP53 at intron 1 and p53 overexpression in primary ECs, but not in the corresponding metastatic lesions.

[DNA adducts in human female genital organs]. / Addukty DNA w narzadach plciowych kobiety.

DNA adducts, one of genetic damages markers, precede and finally can lead to oncogenic mutations. They appear in genome as a result of DNA bases damages caused by various and numerous environmental factors eg. ultraviolet light, ionic radiation, toxins and also endogenic substances, for example estrogens. It is believed that the creation of DNA adducts is a necessary but insufficient process for the neoplastic transformation of the cell. The following review presents concise knowledge about the DNA adducts creation and their sequels served in healthy and cancerous tissues of the female genital organs, on the base of the available data.