Aflatoxin B₁-Induced Developmental and DNA Damage in Caenorhabditis Elegans

Overview

Journal Toxins (Basel)

Publisher MDPI

Specialty Toxicology

Date 2016 Dec 31

PMID 28035971

Citations 10

Authors

Wei-Hong Feng

Kathy S Xue

Lili Tang

Phillip L Williams

Jia-Sheng Wang

Affiliations

Soon will be listed here.

Abstract

Aflatoxin B₁ (AFB₁) is a ubiquitous mycotoxin produced by toxicogenic species. AFB₁ has been reported to cause serious adverse health effects, such as cancers and abnormal development and reproduction, in animals and humans. AFB₁ is also a potent genotoxic mutagen that causes DNA damage in vitro and in vivo. However, the link between DNA damage and abnormal development and reproduction is unclear. To address this issue, we examined the DNA damage, germline apoptosis, growth, and reproductive toxicity following exposure to AFB₁, using as a study model. Results found that AFB₁ induced DNA damage and germline apoptosis, and significantly inhibited growth and reproduction of the nematodes in a concentration-dependent manner. Exposure to AFB₁ inhibited growth or reproduction more potently in the DNA repair-deficient nematodes than the wild-type N2 strain. According to the relative expression level of pathway-related genes measured by real-time PCR, the DNA damage response (DDR) pathway was found to be associated with AFB₁-induced germline apoptosis, which further played an essential role in the dysfunction of growth and reproduction in .

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References

Bischof L, Huffman D, Aroian R . Assays for toxicity studies in C. elegans with Bt crystal proteins. Methods Mol Biol. 2006; 351:139-54. DOI: 10.1385/1-59745-151-7:139. View

Leelaja B, Rajini P . Biochemical and physiological responses in Caenorhabditis elegans exposed to sublethal concentrations of the organophosphorus insecticide, monocrotophos. Ecotoxicol Environ Saf. 2013; 94:8-13. DOI: 10.1016/j.ecoenv.2013.04.015. View

DVORACKOVA I, Stora C, Ayraud N . Evidence of aflatoxin B1 in two cases of lung cancer in man. J Cancer Res Clin Oncol. 1981; 100(2):221-4. DOI: 10.1007/BF00403368. View

Al-Hammadi S, Marzouqi F, Al-Mansouri A, Shahin A, Al-Shamsi M, Mensah-Brown E . The cytotoxicity of aflatoxin b1 in human lymphocytes. Sultan Qaboos Univ Med J. 2014; 14(1):e65-71. PMC: 3916279. DOI: 10.12816/0003338. View

Dhanapal J, Ravindrran M, Baskar S . Toxic effects of aflatoxin B1 on embryonic development of zebrafish (Danio rerio): potential activity of piceatannol encapsulated chitosan/poly (lactic acid) nanoparticles. Anticancer Agents Med Chem. 2014; 15(2):248-57. DOI: 10.2174/1871520614666141016165057. View

Wang J, Groopman J . DNA damage by mycotoxins. Mutat Res. 1999; 424(1-2):167-81. DOI: 10.1016/s0027-5107(99)00017-2. View

Cagnol S, Chambard J . ERK and cell death: mechanisms of ERK-induced cell death--apoptosis, autophagy and senescence. FEBS J. 2009; 277(1):2-21. DOI: 10.1111/j.1742-4658.2009.07366.x. View

Kodoyianni V, Maine E, Kimble J . Molecular basis of loss-of-function mutations in the glp-1 gene of Caenorhabditis elegans. Mol Biol Cell. 1992; 3(11):1199-213. PMC: 275687. DOI: 10.1091/mbc.3.11.1199. View

Kaletta T, Hengartner M . Finding function in novel targets: C. elegans as a model organism. Nat Rev Drug Discov. 2006; 5(5):387-98. DOI: 10.1038/nrd2031. View

10.

Madrigal-Santillan E, Morales-Gonzalez J, Vargas-Mendoza N, Reyes-Ramirez P, Cruz-Jaime S, Sumaya-Martinez T . Antigenotoxic studies of different substances to reduce the DNA damage induced by aflatoxin B(1) and ochratoxin A. Toxins (Basel). 2011; 2(4):738-57. PMC: 3153197. DOI: 10.3390/toxins2040738. View

11.

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

12.

Brenner S . The genetics of Caenorhabditis elegans. Genetics. 1974; 77(1):71-94. PMC: 1213120. DOI: 10.1093/genetics/77.1.71. View

13.

Stergiou L, Hengartner M . Death and more: DNA damage response pathways in the nematode C. elegans. Cell Death Differ. 2003; 11(1):21-8. DOI: 10.1038/sj.cdd.4401340. View

14.

Leung M, Goldstone J, Boyd W, Freedman J, Meyer J . Caenorhabditis elegans generates biologically relevant levels of genotoxic metabolites from aflatoxin B1 but not benzo[a]pyrene in vivo. Toxicol Sci. 2010; 118(2):444-53. PMC: 2984530. DOI: 10.1093/toxsci/kfq295. View

15.

Wood R . DNA damage recognition during nucleotide excision repair in mammalian cells. Biochimie. 1999; 81(1-2):39-44. DOI: 10.1016/s0300-9084(99)80036-4. View

16.

Gumienny T, LAMBIE E, Hartwieg E, Horvitz H, Hengartner M . Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline. Development. 1999; 126(5):1011-22. DOI: 10.1242/dev.126.5.1011. View

17.

Leung M, Williams P, Benedetto A, Au C, Helmcke K, Aschner M . Caenorhabditis elegans: an emerging model in biomedical and environmental toxicology. Toxicol Sci. 2008; 106(1):5-28. PMC: 2563142. DOI: 10.1093/toxsci/kfn121. View

18.

Tam A, Foley J, Devereux T, Maronpot R, Massey T . High frequency and heterogeneous distribution of p53 mutations in aflatoxin B1-induced mouse lung tumors. Cancer Res. 1999; 59(15):3634-40. View

19.

Raj H, Kohli E, Rohil V, Dwarakanath B, Parmar V, Malik S . Acetoxy-4-methylcoumarins confer differential protection from aflatoxin B(1)-induced micronuclei and apoptosis in lung and bone marrow cells. Mutat Res. 2001; 494(1-2):31-40. DOI: 10.1016/s1383-5718(01)00176-0. View

20.

Hunter S, Jung D, Di Giulio R, Meyer J . The QPCR assay for analysis of mitochondrial DNA damage, repair, and relative copy number. Methods. 2010; 51(4):444-51. PMC: 2912960. DOI: 10.1016/j.ymeth.2010.01.033. View