microcystin and Colorectal-Neoplasms

It has been shown by epidemiological and animal studies that microcystin is an important exogenous factor involved in the carcinogenesis of colorectal cancer (CRC). However, details of the mechanism remain unclear. Transformation of colorectal cells is an important initial step in carcinogenesis. Whether microcystin is capable of transforming immortalized colorectal crypt cells, and what the mechanism might be, was investigated. In the present study, we demonstrated that immortalized colorectal crypt cells could be transformed by microcystin. Transformed colorectal crypt cells showed an anchorage-independent growth phenotype, and the proliferation activities of microcystin-transformed cells were also greater than that of immortalized colorectal crypt cells. The Akt and the p38, JNK of mitogen-activated protein kinase (MAPK) pathways in microcystin-transformed cells were found to be constitutively activated. In microcystin-transformed cells, PI3K, MAPKAPK2, Akt, cyclin D1 and cyclin D3 in the Akt pathway; IQGAP-2, RabGTPase, Rap1GAP, RasGAP, R-Ras, Krev-1 and TC21 of the Ras GTP/GDP protein family; and A-Raf, B-Raf and PAK in the Ras/MAPK pathway were all markedly upregulated. However, in positive control cells, dimethylhydrazine-transformed cells, only the Akt pathway was activated by PI3K, and no evidence of alteration of any molecules of the Ras superfamily was observed. Inhibition of Akt, p38 and JNK activation led to a reduced proliferation of microcystin-transformed cells. This implies that the constitutive activation of Akt and the p38, JNK of MAPK pathways in microcystin-transformed cells may be the mechanism by which this important external factor acts in the carcinogenesis of CRC.

Topics: Cell Culture Techniques; Cell Proliferation; Cell Transformation, Neoplastic; Colon; Colorectal Neoplasms; Humans; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase 4; Microcystins; Mitogen-Activated Protein Kinase Kinases; p38 Mitogen-Activated Protein Kinases; Peptides, Cyclic; Precancerous Conditions; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Rectum

To investigate the association of microcystin (MC) in drinking water with the incidence of colorectal cancer.. The study was designed as a retrospective cohort. Eight townships or towns were randomly selected as the study sites in Haining City of Zhejiang Province, China. 408 cases of colon and rectum carcinomas diagnosed from 1977 to 1996 in the study sites were included, and a survey on types of drinking water of these patients was conducted. Samples of different water sources (well, tap, river and pond) were collected separately and microcystin concentrations were determined by indirect competitive ELISA method.. The incidence rate of colorectal cancer was significantly higher in population who drank river and pond water than those who drank well and tap water. Compared to well water, the relative risk (RR) for colorectal cancer was 1.88 (tap), 7.94 (river) and 7.70 (pond) respectively. The positive rate (> 50 pg/mL) of microcystin in samples of well, tap, river and pond water was 0, 0, 36.23% and 17.14% respectively. The concentration of microcystin in river and pond water was significantly higher than that in well and tap water (P < 0.01). Spearman rank correlation analysis showed that in the study sites, the microcystin concentration of river and pond water was positively associated with the incidence of colorectal cancer (rs = 0.881, P < 0.01).. The types of drinking water are positively associated with the incidence of colorectal cancer in the study sites, and this may be related to microcystin contamination of drinking water. Further biological study is needed to support the possible causative role of mycrocystin in carcinogenesis of colon and rectum.

Topics: Bacterial Toxins; Carcinogens, Environmental; China; Cohort Studies; Colorectal Neoplasms; Female; Humans; Male; Microcystins; Peptides, Cyclic; Retrospective Studies; Water; Water Pollutants, Chemical; Water Supply

To assess the relationship between microcystins (a blue-green algal toxin) in drinking water and colorectal cancer.. Eight townships were randomly selected as study sites in Haining city of Zhejiang province, China. Four hundred and eight colon and rectum carcinoma cases diagnosed from 1977 to 1996 were identified from cancer registry in the study sites. A retrospective survey on types of drinking water of all 408 cases was conducted. Population data and drinking water sources data were provided by local household registration and local health institution, respectively. Water samples from different sources (well, tap-water, river and pond) were collected and microcystins concentrations were measured by an indirect competitive ELISA method.. The incidence rates of colorectal cancer were significantly higher among people drinking river or pond water than those who drank well water or tap-water in both males and females. And comparing with other sources to well water, the relative risks (RR) were much higher for people using river water (7.94) and pond water (7.70). The positive detection rates (> 50 pg/ml) of microcystin in well, tap-water, river and pond water were 0.00%, 0.00%, 36.23% and 17.14% respectively. The highest concentrations of microcystins were 1 083.43 pg/ml (river) and 1 937.94 pg/ml (pond) in the positive samples. Microcystins concentrations in river and pond were significantly higher than the concentrations in well and tap water (P < 0.01). The Spearman rank correlation analysis showed that in the study sites, the microcystins concentrations of river and pond water were positively correlated with the incidence of colorectal cancer (r = 0.881, P < 0.01).. Drinking surface water (river or pond) is one of the risk factors for colorectal cancer. Microcystins may be associated with incidence of colorectal cancer. It is suggested that further study should be carried out to clarify the relationship between colorectal cancer and microcystin in drinking water.

Topics: Bacterial Toxins; Carcinogens; China; Colorectal Neoplasms; Enzyme-Linked Immunosorbent Assay; Humans; Incidence; Microcystins; Peptides, Cyclic; Retrospective Studies; Risk Factors; Water Pollutants, Chemical; Water Supply