Cyanobacterial toxins and liver cancer
Bibliographic record
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world today. Over the past decade, the incidence of HCC in Canada has been increasing despite efforts to mitigate disease causing factors such as viral hepatitis B and C infection. Fresh water cyanobacteria are known to release potent hepatotoxins, such as microcystin-LR (MCLR), into drinking and recreational water sources, which have been associated with liver toxicity and HCC. Despite government efforts to limit MCRL contamination, chronic low-dose exposure continues to occur. The purpose of this thesis was to gain an understanding of the potential relationship between chronic low-dose MCLR exposure and HCC. The research contains five areas of investigation; 1) In vitro effects of low-dose MCLR exposure on various hepatocellular cell types, 2) in vitro effects of low-dose MCLR exposure on hepatic stellate cells and fibrosis, 3) in vivo effects of chronic low-dose MCLR exposure on HCC initiation and promotion, 4) in vivo effects of chronic low-dose MCLR exposure on hepatic fibrosis and 5) national and provincial epidemiological analysis investigating the potential association between cyanobacterial hepatotoxins and liver cancer. Our methodology involved; 1) exposing WB-F344, PLC and CFSC-2G hepatic cell lines to varying concentrations of MCLR and observing changes in cell proliferation, protein expression, wound healing and malignant transformation, 2) continuously exposing adult male mice to 1 µg/L of MCLR in their drinking water for seven months, and observing changes in body weight, liver histology, liver enzymes, hepatic fibrosis and HCC development, 3) conducting a national HCC epidemiological study, and determining the relative risk of developing HCC from up-stream factors contributing to cyanobacterial contamination of drinking water sources and 4) conducting a provincial epidemiological study that involved collecting liver cancer incidence data from the Manitoba cancer registry from 1985 to 2007, and temporally and spatially analyzing the association between cancer incidence and MCLR measured in Manitoba lakes. The in vitro results indicate that chronic low-dose exposure to MCLR does not significantly induce cellular characteristics associated with a malignant and/or pro-fibrotic phenotype. In vivo, there were no significant changes in liver pathology, plasma chemistry, histology or tumor development compared to negative controls. Epidemiological analyses conducted at the national and provincial levels revealed similar trends. HCC incidence in Canada was associated with urban residence, immigration and hepatitis B. However, HCC incidence was not found to be influenced by the up-stream cyanobacterial predictive factors; agriculture, cattle and swine density. In Manitoba, the increasing incidence of liver cancer did not temporally or spatially associate with MCLR contamination sites within the province. In conclusion, these results are reassuring in that they suggest that chronic low-dose exposure to MCLR does not initiate or promote the development of HCC at the cellular, systemic or epidemiological levels.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".