Cyanobacterial toxins and liver cancer
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».