Benzo[a]pyrene induced p53-mediated cell cycle arrest, DNA repair, and apoptosis pathways in Chinese rare minnow (Gobiocypris rarus).
The p53 pathways play an important role in carcinogenesis. In mammals, p53 and p53 target genes have been extensively studied, but little is known about their functions and regulation in fish. In this study, the cDNA fragments of p53 network genes, including p53, p21, mdm2, gadd45α, gadd45β, igfbp-3, and bax, were cloned from Chinese rare minnow (Gobiocypris rarus). These genes displayed high amino acid sequence identities with their zebrafish orthologs. The mRNA levels of p53 network genes and pathological changes in the liver were determined after adult rare minnow were exposed to 0.4, 2, and 10 µg/L of benzo[a]pyrene (BaP) for 28 days. The results showed that p53, p21, mdm2, gadd45α, and bax mRNA expressions in the livers from males and females were significantly upregulated compared with those of the controls (p < 0.05), but gadd45β and igfbp-3 expression was not significantly changed. Microphotographs revealed enlargement of the cell nuclei and cellular degeneration in males, while atrophy and vacuolization of hepatocytes were observed in females (10 µg/L). These results suggested that BaP induced liver DNA repair and apoptosis pathways and caused adverse pathological changes in rare minnow. The strongly responsive p53 network genes in the livers suggest that rare minnow is suitable as an experimental fish to screen environmental carcinogens. In addition, the p53 network genes in rare minnow could feasibly be used to identify the mechanism of environmental carcinogenesis. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 979-988, 2017.
Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.
Lilai
L
Yuan
Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.
Biping
B
Lv
Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.|Beijing Key Laboratory of Industrial Wastewater Treatment and Reuse, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.
Jinmiao
J
Zha
Beijing Key Laboratory of Industrial Wastewater Treatment and Reuse, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.|State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.
Zijian
Z
Wang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D003530:Cyprinidae / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics; D005260:Female; D053263:Gene Regulatory Networks / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D016159:Tumor Suppressor Protein p53; D014874:Water Pollutants, Chemical; D001564:Benzo(a)pyrene
benzo[a]pyrene; gene expression; histopathology; p53 network genes; rare minnow (Gobiocypris rarus)