Induction of Micronuclei, Cellular Stress Response, and DNA Strand Breakage in Two Common Fish Species From Rivers and Reservoirs in Ilorin, Nigeria.

Abstract Indiscriminate discharge of home, agricultural, and industrial wastes into water bodies, most rivers and reservoirs around the world are becoming polluted. The ecotoxicological potential of this in fish species gathered from important reservoirs and rivers in Ilorin, Nigeria, was explored in this study. Unilorin reservoir, Asa reservoir, Apodu reservoir, Asa river (Unity), and Asa river (Unity) water samples were collected and physicochemical characteristics were investigated at five distinct sites: Unilorin reservoir, Asa reservoir, Apodu reservoir, Asa river (Unity), and Asa river (Unity) (Harmony). In Tilapia zillii and Clarias gariepinus, we measured serum biochemical (AST, ALT, ALP, serum ALB), histopathological (gills, lungs), and serum antioxidant enzyme responses (SOD, CAT, GPx, GR, GST) as a biomarker for oxidative stress, while micronucleus and comet assays were used to detect DNA damage. Except for DO, which was very low in the two rivers, the physicochemical parameters and heavy metals evaluated in the five separate water bodies were within the allowed levels of the NSDWQ and WHO standard for drinking water. In comparison to the Unilorin, Apodu, and Asa reservoirs, a slight increase in Pb was observed across the five sampling sites, which could contribute to increased biochemical and haematological profiles, histopathological lesions in the gill and lungs, inductions of MN, NA, and DNA single strand break in T. zillii and C. gariepinus collected from Asa rivers. This could be due to the indiscriminate dumping of effluents from adjacent industries, agricultural wastes, and household wastes into rivers.

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Cellular stress response, induction of micronuclei and DNA strand breaks in two common fish species of Rivers and Reservoirs in Ilorin, North Central, Nigeria.

10.21203/rs.3.rs-172188/v1 ◽

2021 ◽

Author(s):

Abass Toba Anifowoshe ◽

Segun Olayinka Oladipo ◽

Arinola N Oyinloye ◽

Augusta Opute ◽

Edward Odofin ◽

...

Keyword(s):

Fish Species ◽

Physicochemical Parameters ◽

Clarias Gariepinus ◽

Water Bodies ◽

Industrial Wastes ◽

Cellular Stress Response ◽

Single Strand Break ◽

North Central ◽

Tilapia Zillii ◽

Rivers And Reservoirs

Abstract Most rivers and reservoirs in the world are prone to pollution because of indiscriminate disposal of domestic, agricultural and industrial wastes into the water bodies. In this study, we investigated the ecotoxicological potential this could pose in fish species collected from major reservoirs and rivers in Ilorin, north central, Nigeria. Water samples were collected and the physicochemical parameters were examined from five different sites; Unilorin reservoir, Asa reservoir, Apodu reservoir, Asa river (Unity) and Asa river (Harmony). We determined serum biochemical (AST, ALT, ALP, serum ALB), histopathological (gill, lungs), serum antioxidant enzyme responses (SOD, CAT, GPx, GR, GST) which serves as a biomarker for evaluating oxidative stress while micronucleus and comet assays were used to detect level of DNA damage in Tilapia zillii and Clarias gariepinus. The physicochemical parameters and heavy metal analysed (Pb, Mn, Cu, Ni, N, P, Fe, Cl, and Ca) in the five different water bodies were below the permissible limits of WHO and USEPA except the DO, which was very low in the two rivers, indicating hypoxia. Our results showed significant increase in biochemical and hematological profiles, histopathological lesions in the gill and lungs, inductions of MN, NA and DNA single strand break in Tilapia zillii and Clarias gariepinus collected from Asa rivers compared to the Unilorin, Apodun and Asa reservoirs. This may be attributed to indiscriminate discharge of effluents from nearby industries, agricultural and domestic wastes into the rivers.

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Aberrant PARP1 Activity Couples DNA Breaks to Deregulated Presynaptic Calcium Signalling and Lethal Seizures

10.1101/431916 ◽

2018 ◽

Cited By ~ 1

Author(s):

Emilia Komulainen ◽

Jack Badman ◽

Stephanie Rey ◽

Stuart Rulten ◽

Limei Ju ◽

...

Keyword(s):

Hippocampal Neurons ◽

Ex Vivo ◽

Calcium Signalling ◽

Strand Break ◽

Parp Inhibition ◽

Dna Breaks ◽

Single Strand Break ◽

Presynaptic Calcium ◽

Dna Strand

AbstractDefects in DNA single-strand break repair result in cerebellar ataxia which in Xrcc1Nes-Cre mice is promoted by hyperactivity of the DNA strand break sensor protein, Parp1. Here, we show that Parp1 hyperactivity extends beyond the cerebellum in Xrcc1-defective brain, resulting in lethal seizures and shortened lifespan. We demonstrate that aberrant Parp1 activation triggers seizure-like activity in Xrcc1-defective hippocampus ex vivo and aberrant presynaptic calcium signalling in isolated hippocampal neurons in vitro. Moreover, we show that these defects are prevented by Parp1 inhibition and/or deletion. Collectively, these data identify aberrant Parp1 activity at unrepaired DNA breaks as a cell-autonomous source of deregulated presynaptic calcium signalling, and highlight PARP inhibition as a possible therapeutic approach in XRCC1-mutated neurodegenerative disease.SummaryPARP1 activity and presynaptic Ca2+ signalling

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Novel PNKP mutations causing defective DNA strand break repair and PARP1 hyperactivity in MCSZ

Neurology Genetics ◽

10.1212/nxg.0000000000000320 ◽

2019 ◽

Vol 5 (2) ◽

pp. e320 ◽

Cited By ~ 5

Author(s):

Ilona Kalasova ◽

Hana Hanzlikova ◽

Neerja Gupta ◽

Yun Li ◽

Janine Altmüller ◽

...

Keyword(s):

Topoisomerase I ◽

Strand Break ◽

Neurologic Disease ◽

Dna Breaks ◽

Novel Mutations ◽

Molecular Feature ◽

Single Strand Break ◽

Dna Strand Break ◽

Break Repair ◽

Dna Strand

ObjectiveTo address the relationship between novel mutations in polynucleotide 5'-kinase 3'-phosphatase (PNKP), DNA strand break repair, and neurologic disease.MethodsWe have employed whole-exome sequencing, Sanger sequencing, and molecular/cellular biology.ResultsWe describe here a patient with microcephaly with early onset seizures (MCSZ) from the Indian sub-continent harboring 2 novel mutations in PNKP, including a pathogenic mutation in the fork-head associated domain. In addition, we confirm that MCSZ is associated with hyperactivation of the single-strand break sensor protein protein poly (ADP-ribose) polymerase 1 (PARP1) following the induction of abortive topoisomerase I activity, a source of DNA strand breakage associated previously with neurologic disease.ConclusionsThese data expand the spectrum of PNKP mutations associated with MCSZ and show that PARP1 hyperactivation at unrepaired topoisomerase-induced DNA breaks is a molecular feature of this disease.

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Mouse CSB protein is important for gene expression in the presence of a single-strand break in the non-transcribed DNA strand

DNA Repair ◽

10.1016/j.dnarep.2010.06.011 ◽

2010 ◽

Vol 9 (9) ◽

pp. 985-993 ◽

Cited By ~ 14

Author(s):

Andriy Khobta ◽

Thomas Lingg ◽

Ina Schulz ◽

Daniela Warken ◽

Nataliya Kitsera ◽

...

Keyword(s):

Gene Expression ◽

Strand Break ◽

Single Strand ◽

Single Strand Break ◽

Dna Strand

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Feeding and Feeding Behavior of Invasive Fish Species in the Water Bodies of the West Polissya of Ukraine

Hydrobiological Journal ◽

10.1615/hydrobj.v47.i1.50 ◽

2011 ◽

Vol 47 (1) ◽

pp. 51-60 ◽

Cited By ~ 1

Author(s):

V. K. Bigun ◽

S. A. Afanasyev

Keyword(s):

Feeding Behavior ◽

Fish Species ◽

Water Bodies ◽

Invasive Fish ◽

The West

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Activated STAT3 Is a Novel Regulator of the XRCC1 Promoter and Selectively Increases XRCC1 Protein Levels in Triple Negative Breast Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22115475 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5475

Author(s):

Griffin Wright ◽

Manoj Sonavane ◽

Natalie R. Gassman

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Excision Repair ◽

Strand Break ◽

Xrcc1 Gene ◽

Single Strand Break ◽

Expression Levels ◽

Constitutive Activation ◽

Gene And Protein Expression

Base Excision Repair (BER) addresses base lesions and abasic sites induced by exogenous and endogenous stressors. X-ray cross complementing group 1 (XRCC1) functions as a scaffold protein in BER and single-strand break repair (SSBR), facilitating and coordinating repair through its interaction with a host of critical repair proteins. Alterations of XRCC1 protein and gene expression levels are observed in many cancers, including colorectal, ovarian, and breast cancer. While increases in the expression level of XRCC1 are reported, the transcription factors responsible for this up-regulation are not known. In this study, we identify the signal transducer and activator of transcription 3 (STAT3) as a novel regulator of XRCC1 through chromatin immunoprecipitation. Activation of STAT3 through phosphorylation at Y705 by cytokine (IL-6) signaling increases the expression of XRCC1 and the occupancy of STAT3 within the XRCC1 promoter. In triple negative breast cancer, the constitutive activation of STAT3 upregulates XRCC1 gene and protein expression levels. Increased expression of XRCC1 is associated with aggressiveness and resistance to DNA damaging chemotherapeutics. Thus, we propose that activated STAT3 regulates XRCC1 under stress and growth conditions, but constitutive activation in cancers results in dysregulation of XRCC1 and subsequently BER and SSBR.

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