Promotion effect of microcystin-LR on liver tumor progression in krasV12 transgenic zebrafish following acute or subacute exposure

• Main Authors: Yuchao Mao, Zijing Zong, Yao Dang, Liqin Yu, Chunsheng Liu, Jianghua Wang
• Format: Article
• Language: English
• Published: Elsevier 2021-11-01
• Series: Ecotoxicology and Environmental Safety
• Subjects: Microcystin-LR; Liver tumor progression; Transgenic zebrafish; Acute and subacute exposure
• Online Access: http://www.sciencedirect.com/science/article/pii/S0147651321007855

Microcystin-LR (MC-LR) is widely distributed in the natural environment and causes hepatotoxicity. However, whether MC-LR promotes liver tumor progression remains controversial. krasV12 transgenic zebrafish were used as an inducible liver tumor model to evaluate the potential tumor-promoting effect of MC-LR. First, krasV12 transgenic larvae were exposed to 0, 0.1 and 1 mg/L MC-LR with 20 mg/L doxycycline (Dox) for 4 d. The gray values and histopathological examinations of the liver demonstrated that MC-LR aggravated liver tumor progression, which could be inhibited by the Protein arginine methyltransferase 5 (Prmt5) inhibitor compound 5 (CMP5). Second, 1-month-old juvenile transgenic zebrafish were exposed to 0, 20 mg/L Dox, 1 μg/L MC-LR, and 20 mg/L Dox with 0.1 or 1 μg/L MC-LR for 15 d to determine whether the exposure to environmental concentrations of MC-LR promoted hepatocellular carcinoma (HCC) progression. We found that environmental concentrations of MC-LR increased the hepatosomatic index (HSI) and gray value (intensity/area) and promoted HCC progression. The results indicate that environmental concentrations of MC-LR have the potential to promote liver tumor progression. Taken together, the present study demonstrates that MC-LR can promote tumor in krasV12 transgenic zebrafish and that the upregulation of prmt5 expression might contribute to MC-LR-mediated promotion of liver tumorigenesis.