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Background: Colorectal cancer is an increasing cause of death. Circulating microRNAs (miRs) could be great diagnostic and prognostic biomarkers of colorectal cancer, but further continuation of their utility is needed for their comprehensive application., Materials and Methods: Twenty-seven patients with colonic cancer, 16 with rectal cancer and 12 healthy volunteers as controls, were involved in this study. Expression of miR-155, miR-21, miR-221, miR-30a, miR-34a and miR-29a were determined by reverse transcription polymerase chain reaction (RT-PCR) from sera of patients., Results: Expression of miR-155, miR-21 and miR-221 was significantly higher in rectal cancer than in colonic cancer. There was no difference found between those with TNM1 cancer and controls for both cancer types. miR-155, miR-34a and miR-29a were down-regulated in all patients with cancer compared to controls. We did not find any statistically significant up-regulation of miR-221 in patients with colonic cancer compared to controls. In contrast, in patients with rectal cancer, miR-221 expression was higher than in controls. Advanced stage was also linked to higher miR-221 expression compared to early stage. Slight, but statistically significant increase was observed in miR-30a expression in patients with colon cancer compared to control individuals., Conclusion: Our results partly support previous findings. Here we report on differences in the expression of circulating microRNA between colonic and rectal tumours for the first time., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Methylnitrosourea (MNU) is a well-known pluripotent direct-acting carcinogen. Formation of MNU following incubation of various meats with additional nitrite under in vitro acidic conditions is possible. It is possible that many species, including humans, are exposed to carcinogenic MNU, generated in their alimentary tract. Previously, an animal model was developed by our research group to investigate the expression of three genes c-myc, Ha-ras and p53 as early molecular epidemiological biomarkers of carcinogenic exposure or carcinogenesis caused by DMBA (dimethylbenz[alpha]anthracene). The aim of this study was to investigate the early effect of MNU on the gene expression levels. MNU is a direct-acting carcinogen which spontaneously and rapidly degrades, so any effect on the gene expression is observed in 24 hours. Our results show the maximum effect in vivo on the gene expression at 12 hours after the MNU treatment; on the other hand, 24 hours after the treatment, the elevated gene expressions decreased in target organs (bone marrow, lung, lymph nodes). Our results correspond to "long-term" experiments of the carcinogenic effect of MNU in different target organs. Our findings suggest that MNU has an impact on the expression of c-myc, Ha-ras and p53 genes in 12 hours, especially in bone marrow. Overexpression of these genes occurs as an early biological effect of exposure to chemical carcinogens. According to our results, the high expression of these genes could indicate MNU exposure and these genes could take part in MNU-induced tumorigenesis.

According to recent publications 7,12-dimethylbenz[a]anthracene (DMBA) induces not only mammary cancer but also leukemia in Long-Evans (LE) rats. After treatment with DMBA, trisomy of the chromosome bearing N-ras and mutations in the codon 61 of different ras family genes are frequent. These alterations are already visible within 48 hours. Since there are very few data on ras genes' expression in the early stages of leukemogenesis, in our investigations LE rats were treated with DMBA and the expression of ras genes was measured within two days. DMBA was administered to outbred Long-Evans rats and the fluorescence intensity of the antibody recognizing the ras gene family was measured in femoral bone marrow cells 24 and 48 hours after the treatment. One of the bone marrow cell populations, separated by FSC and SSC, showed elevated ras gene expression at both 24 and 48 hours after the administration of the carcinogen. These results suggest that, besides the specific chromosomal aberrations and gene mutations, elevated ras gene expression could also be the marker of DMBA exposure.

The aim of the study was to monitor the early effect of cytostatics containing platinum on oncogenes in inbred CBA/Ca mice. In human head-neck tumors after treatment with the Cisplatin supplemented BVM (Bleomycin, Vincristine, Methotrexate) protocol, further surgeries are often necessary due to regional recurrence. Body weight equivalent amounts of human dose of Cisplatin were administered intraperitoneally to 6-8-week-old, inbred, female CBA/Ca mice. Twenty four 48 and 72 hours after the treatment RNA was isolated from the target organs and the quantitative expression of c-myc, Ha-ras and p53 genes was examined by dot-blotting in potential target tissues. Significant overexpression of Ha-ras and p53 genes was measured in the bone marrow. Regarding the expression of Ha-ras gene, a significant increase was also found in the lymph nodes after 48 hours. The p53 expression in the lungs was down-regulated compared to the control group. In the "short-term" in vivo test, 24-hour examination of gene expression and amplification is suitable for detecting the early effects of carcinogenetic exposure. Cisplatin-induced gene expression alterations call attention to its possible role in the development of regional recurrence in patients treated with cisplatin-containing regimens.

An understanding of the molecular changes occuring during exposure to a carcinogen enhances the possibility of cancer prevention. Molecular genetic-biological screening methods offer the potential for early diagnosis of high-risk groups, and identification of specific signals, as a major step in primary prevention. Recent investigations have suggested that oncogene or oncosuppressor gene expression investigation at the RNA level is a proper and early molecular epidemiological biomarker of carcinogen exposure and a tool for risk assessment. This is one way by which the high-risk groups could be recognized. At the protein level, the investigation of gene expression is very useful in molecular diagnosis and in molecular pathology.

Autooxidation of polyunsaturated fatty acids (PUFAs) of edible oils results in the formation of fatty acid hydroperoxides that can undergo further chemical transformations to yield a variety of re-arranged and chain-cleavage products. Since the oxidation products of PUFAs have been reported to have cytotoxic and mutagenic effects, the consumption of rancid oils and fats represents a possible health hazard for the population. Storage of corn oil at room temperature and in the refrigerator for a forty-eight month period resulted in two different qualities of oil samples, which were characterized by UV, titrimetric (peroxide value, acid value) and GC-MS methods. Earlier it was demonstrated that the increase of expression of certain oncogenes and tumor suppressor genes is a method of choice for the early detection of carcinogen exposure. Treatment of CBA/Calpha inbred mice with the two oil samples showed significantly increased expression of the Ha-ras gene in all the investigated organs (liver, lung, kidney, thymus and spleen) of the rancid corn oil-treated animals. Expression of the c-myc and the p53 genes was also increased after the rancid corn oil-treatment in all the organs but the thymus of the mice. The results suggest that rancid oils, rich in omega-6 unsaturated fatty acids, could be involved not only in tumor promotion but in initiation as well.