Fish p53 as a possible biomarker for genotoxins in the aquatic environment

Bhaskaran, A; May, Denise; Rand‐Weaver, Mariann; Tyler, Charles R.

doi:10.1002/(sici)1098-2280(1999)33:3<177::aid-em1>3.3.co;2-o

Cited by 9 publications

(10 citation statements)

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“…This suggests that the gene duplication event that generated adjacent INK4A and INK4B genes occurred after the divergence of the lineage leading to mammals from ®sh *450 million years ago. Genes encoding p53 and pRb have now been identi®ed in ®sh (Brunelli and Thorgaard, 1999;Bhaskaran et al, 1999), and our inability to ®nd an ARF-like ®rst exon associated with the Fugu INK4A/B gene indicates that the Fugu pRb and p53 pathways are not regulated by a single locus (as in mammals). Either ARF is not coded for in Fugu (perhaps unlikely given its importance in mammals), or it is encoded by a gene that is independent of an INK4 gene.…”

Section: Resultsmentioning

confidence: 97%

One INK4 gene and no ARF at the Fugu equivalent of the human INK4A/ARF/INK4B tumour suppressor locus

Gilley

Fried

2001

Oncogene

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The INK4A/ARF/INK4B locus, conserved in mammals, encodes three polypeptides that regulate cell proliferation via the pRb and p53 tumour suppressor pathways. The locus is mutated in many cancers. The related, tandemlylinked INK4A and INK4B genes encode the p16 INK4A and p15 INK4B members of the INK4 family of cyclin-dependent kinase inhibitors which block phosphorylation of pRb, whereas the third product, ARF, derived from an alternative reading frame of INK4A, regulates p53 activity. We assessed the status of this unusual locus in the pu er ®sh, Fugu rubripes, and identi®ed two INK4 genes using degenerate PCR and hybridization analyses. Sequence conservation and conservation of synteny between human and Fugu predict one gene to be an INK4A or INK4B homologue and the other an INK4D homologue. Analysis of the Fugu INK4A/B gene and the surrounding 40-kb of genomic DNA did not reveal the presence of any ARF-encoding potential or another related INK4 gene. We conclude that the gene duplication event that generated adjacent INK4A and INK4B genes and the association of ARF with the ancestral INK4A gene occurred after the divergence of the lineage leading to mammals from ®sh. Thus, unlike mammals, the ®sh p53 and pRb tumour suppressor pathways are not regulated by a single locus. Oncogene (2001) 20, 7447 ± 7452.

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Section: Resultsmentioning

confidence: 97%

One INK4 gene and no ARF at the Fugu equivalent of the human INK4A/ARF/INK4B tumour suppressor locus

Gilley

Fried

2001

Oncogene

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“…S2). Among these species, both X. hellerii and L. forbesi live in hypoxic aquatic environments (7), and T. miurus lives on sandy bottoms in deep water (45). P. flesus is also known to be moderately tolerant of hypoxia (46,47).…”

Section: Resultsmentioning

confidence: 99%

Codon 104 variation of p53 gene provides adaptive apoptotic responses to extreme environments in mammals of the Tibet plateau

Zhao

Wang

Zhang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Mutational changes in p53 correlate well with tumorigenesis. Remarkably, however, relatively little is known about the role that p53 variations may play in environmental adaptation. Here we report that codon asparagine-104 (104N) and glutamic acid-104 (104E), respectively, of the p53 gene in the wild zokor (Myospalax baileyi) and root vole (Microtus oeconomus) are adaptively variable, meeting the environmental stresses of the Tibetan plateau. They differ from serine-104 (104S) seen in other rodents, including the lowland subterranean zokor Myospalax cansus, and from serine 106 (106S) in humans. Based on site-directed mutational analysis in human cell lines, the codon 104N variation in M. baileyi is responsible for the adaptive balance of the transactivation of apoptotic genes under hypoxia, cold, and acidic stresses. The 104E p53 variant in Microtus oeconomus suppresses apoptotic gene transactivation and cell apoptosis. Neither 104N nor 104E affects the cell-cycle genes. We propose that these variations in p53 codon 104 are an outcome of environmental adaptation and evolutionary selection that enhance cellular strategies for surviving the environmental stresses of hypoxia and cold (in M. baileyi and M. oeconomus) and hypercapnia (in M. baileyi) in the stressful environments of the Qinghai-Tibet plateau.T he regulatory mechanisms of p53 mutation related to tumorigenesis have been widely studied and elucidated (1, 2). Notably, however, p53 evolution and adaptation to environmental stresses have not attracted as much attention. Current studies show that p53 is a master sensor and regulator in response to various stressors, such as DNA damage and hypoxia (3-6). Activation of p53 by stresses results in cell-cycle arrest, DNA repair, senescence, or apoptosis in which a series of p53 target genes are involved to maintain genomic integrity (2). The p53 variations associated with environmental stresses have been described in the Mexican salamander axolotl Ambystoma mexicanum and the Israeli blind subterranean mole rat (Spalax judaei; hereafter, S.j.) (7-9).For animals existing on high plateaus, hypoxia and cold serve as strong environmental selective pressures generating adaptive complexes to cope with these stresses. Animals that have evolved on plateaus adopt various strategies involving multiple variations to regulate a series of genes (3, 7). The zokor (Myospalax baileyi, Thomas, 1911; hereafter M.b.) and root vole (Microtus oeconomus, Pallas, 1776; hereafter M.o.) are the dominant native mammals living on the alpine meadow of the Qinghai-Tibet Plateau of China at altitudes of 3,000-4,500 m (equivalent to 11.0-13.0% O 2 at sea level). M.b. is genetically close to Myospalax cansus (Lyon, 1907; hereafter, M.c.), which lives in subterranean burrows at a lower altitude of about 800 m in the lowland of western China. M.b. and M.c. spend their entire life cycle at 70-250 cm underground with significantly low O 2 and high CO 2 levels in their burrows (10). Since the collision of the Indian and the Eurasian plates during the...

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“…ADE21938; Bhaskaran et al 1999). In contrast, the amino acid identity between the entire flounder and human P53 sequences is only 38% (Cachot et al 1998), suggesting differences in P53 protein structure and therefore possible differences in biological functions (Cachot et al 2004;Chen et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional responses of cancer-related genes in turbot Scophthalmus maximus and mussels Mytilus edulis exposed to heavy fuel oil no. 6 and styrene

et al. 2012

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Recent spills in European waters have released polycyclic aromatic hydrocarbons, important components of heavy fuel oil, and the hydrocarbon styrene. Heavy fuel oil and styrene are classified as potentially genotoxic and carcinogenic. Here we investigate transcription of genes involved in cancer development in the liver of juvenile turbots and in the digestive gland of mussels exposed to heavy fuel oil and to styrene and after a recovery period. In turbot, oil produced a significant up-regulation of p53 and gadd45α after 14 days exposure. cyclin G1 was up-regulated after 7 days treatment with styrene. In mussels, ras was down-regulated in both treatments after the recovery periods. No mutations in ras hotspots were detected in exposed mussels. gadd45α was up-regulated after the recovery period of the styrene experiment. Overall, transcriptional responses differed in mussels compared to turbot. Turbot responded to hydrocarbon exposure by triggering cell cycle arrest (p53) and DNA repair (gadd45α).

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Fish p53 as a possible biomarker for genotoxins in the aquatic environment

Cited by 9 publications

References 0 publications

One INK4 gene and no ARF at the Fugu equivalent of the human INK4A/ARF/INK4B tumour suppressor locus

One INK4 gene and no ARF at the Fugu equivalent of the human INK4A/ARF/INK4B tumour suppressor locus

Codon 104 variation of p53 gene provides adaptive apoptotic responses to extreme environments in mammals of the Tibet plateau

Transcriptional responses of cancer-related genes in turbot Scophthalmus maximus and mussels Mytilus edulis exposed to heavy fuel oil no. 6 and styrene

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