Environmental Science and Pollution Research

, Volume 26, Issue 15, pp 15124–15135 | Cite as

Modified CDKN2B (p15) and CDKN2A (p16) DNA methylation profiles in urban pesticide applicators

  • José Francisco Herrera-Moreno
  • Irma Martha Medina-Díaz
  • Yael Yvette Bernal-Hernández
  • Kenneth S. Ramos
  • Isabel Alvarado-Cruz
  • Betzabet Quintanilla-Vega
  • Cyndia Azucena González-Arias
  • Briscia Socorro Barrón-Vivanco
  • Aurora Elizabeth Rojas-GarcíaEmail author
Research Article


Gene-specific changes in DNA methylation by pesticides in occupationally exposed populations have not been studied extensively. Of particular concern are changes in the methylation profile of tumor-suppressor, such as CDKN2B and CDKN2A, genes involved in oncogenesis. The aim of this study was to evaluate the methylation profiles of CDKN2B and CDKN2A genes in urban pesticide applicators and their relationship with occupational exposure to pesticides. A cross-sectional study was conducted in 186 urban pesticide applicators (categorized as high or moderate exposures) and 102 participants without documented occupational exposures to pesticides. Acute and chronic pesticide exposures were evaluated by direct measurement of urinary dialkylphosphates, organophosphate metabolites, and a structured questionnaire, respectively. Anthropometric characteristics, diet, clinical histories, and other variables were estimated through a validated self-reported survey. DNA methylation was determined by pyrosequencing of bisulfite-treated DNA. Decreased DNA methylation of the CDKN2B gene was observed in pesticide-exposed groups compared to the non-exposed group. In addition, increased methylation of the CDKN2A promoter was observed in the moderate-exposure group compared to the non-exposed group. Bivariate analysis showed an association between CDKN2B methylation and pesticide exposure, general characteristics, smoking status, and micronutrients, while changes in CDKN2A methylation were associated with pesticide exposure, sex, educational level, body mass index, smoking status, supplement intake, clinical parameters, and caffeine consumption. These data suggest that pesticide exposure modifies the methylation pattern of CDKN2B and CDKN2A genes and raise important questions about the role that these changes may play in the regulation of cell cycle activities, senescence, and aging.


Pesticides Gene-specific methylation CDKN2B CDKN2A 



We are grateful to all the workers who participated in the study. The authors also thank Dr. Leticia Yáñez-Estrada and her team at the Autonomous University of San Luis Potosí, Mexico, for measurements of DAP.

Funding sources

This work was supported by CONACyT (Grant #233803).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest to report.


  1. (WHO) World Health Organization (2006) BMI classification. Global database on body mass index. [on line]. Accessed 3 Apr 2018
  2. Alvarado-Cruz I, Sánchez-Guerra M, Hernández-Cadena L, de Vizcaya-Ruiz A, Mugica V, Pelallo-Martínez NA, Solís-Heredia MJ, Byun HM, Baccarelli A, Quintanilla-Vega B (2017) Increased methylation of repetitive elements and DNA repair genes is associated with higher DNA oxidation in children in an urbanized, industrial environment. Mutat Res 813:27–36. CrossRefGoogle Scholar
  3. Andre V, Le Goff J, Pottier D et al (2007) Evaluation of bulky DNA adduct levels after pesticide use: comparison between open-field farmers and fruit growers. Toxicol Environ Chem 89(1):125–139. CrossRefGoogle Scholar
  4. Andreotti G, Karami S, Pfeiffer RM et al (2014) LINE1 methylation levels associated with increased bladder cancer risk in pre-diagnostic blood DNA among US (PLCO) and European (ATBC) cohort study participants. Epigenetics 3:404–415. CrossRefGoogle Scholar
  5. Anway MD, Leathers C, Skinner MK (2006) Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease. Endocrinology 147(12):5515–5523. CrossRefGoogle Scholar
  6. Azad M, Kaviani S, Noruzinia M et al (2013) Expression status and methylation pattern in promoter of P15INK4b and P16INK4a in cord blood CD34+ stem cells. Iran J Basic Med Sci 16:822–828Google Scholar
  7. Azad M, Goudarzi M, Sahmani M et al (2015) Correlation between methylation and expression level of P15 and P16 genes during differentiation of cord blood stem cells into erythroid lineage mediated by erythropoietin. Novel Biomed 1:6–12Google Scholar
  8. Baccarelli A, Bollati V (2009) Epigenetics and environmental chemicals. Curr Opin Pediatr 2:243–251CrossRefGoogle Scholar
  9. Bachman KE, Park BH, Rhee I, Rajagopalan H, Herman JG, Baylin SB, Kinzler KW, Vogelstein B (2003) Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene. Cancer Cell 3:89–95CrossRefGoogle Scholar
  10. Barchitta M, Quattrocchi A, Maugeri A, Vinciguerra M, Agodi A (2014) LINE-1 hypomethylation in blood and tissue samples as an epigenetic marker for cancer risk: a systematic review and meta-analysis. PLoS One 9(10):e109478. CrossRefGoogle Scholar
  11. Baylin SB, Herman JG (2000) DNA hypermethylation in tumorigenesis: epigenetics joins genetics. Trends Genet 16(4):168–174CrossRefGoogle Scholar
  12. Benedetti D, Lopes Alderete B, Telles de Souza C et al (2017) DNA damage and epigenetic alteration in soybean farmers exposed to complex mixture of pesticides. Mutagenesis 33(1):87–95CrossRefGoogle Scholar
  13. Benitez-Trinidad AB, Herrera-Moreno JF, Vázquez-Estrada G, Verdín-Betancourt FA, Sordo M, Ostrosky-Wegman P, Bernal-Hernández YY, Medina-Díaz IM, Barrón-Vivanco BS, Robledo-Marenco ML, Salazar AM, Rojas-García AE (2015) Cytostatic and genotoxic effect of temephos in human lymphocytes and HepG2 cells. Toxicol in Vitro 29(4):779–786. CrossRefGoogle Scholar
  14. Benitez-Trinidad AB, Medina-Díaz IM, Bernal-Hernández YY, Barrón-Vivanco BS, González-Arias CA, Herrera-Moreno JF, Alvarado-Cruz I, Quintanilla-Vega B, Rojas-García AE (2018) Relationship between LINE-1 methylation pattern and pesticide exposure in urban sprayers. Food Chem Toxicol 113:125–133. CrossRefGoogle Scholar
  15. Boultwood J, Wainscoat JS (2007) Gene silencing by DNA methylation in haematological malignancies. Br J Haematol 138(1):3–11. CrossRefGoogle Scholar
  16. Brennan K, Flanagan JM (2012) Is there a link between genome-wide hypomethylation in blood and cancer risk? Cancer Prev Res (Phila) 12:1345–1357. CrossRefGoogle Scholar
  17. Bull S, Fletcher K, Boobis AR, Battershill JM (2006) Evidence for genotoxicity of pesticides in pesticide applicators: a review. Mutagenesis 21(2):93–103. CrossRefGoogle Scholar
  18. Chen ML, Chang JH, Yeh KT, Chang YS, Chang JG (2007) Epigenetic changes in tumor suppressor genes, P15, P16, APC-3 and E-cadherin in body fluid. Kaohsiung J Med Sci 23(10):498–503CrossRefGoogle Scholar
  19. Chinaranagari S, Sharma P, Bowen NJ, Chaudhary J (2015) Prostate cancer epigenome. Methods Mol Biol 1238:125–140. CrossRefGoogle Scholar
  20. Christman JK (2002) 5-Azacytidine and 5-aza-2′-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapy. Oncogene 21(35):5483–5495. CrossRefGoogle Scholar
  21. Collotta M, Bertazzi PA, Bollati V (2013) Epigenetics and pesticides. Toxicology 307:35–41. CrossRefGoogle Scholar
  22. Csankovszki G, Nagy A, Jaenisch R (2001) Synergism of Xist RNA, DNA methylation, and histone hypoacetylation in maintaining X chromosome inactivation. J Cell Biol 153(4):773–784CrossRefGoogle Scholar
  23. Dansranjavin T, Krehl S, Mueller T, Mueller LP, Schmoll HJ, Dammann RH (2009) The role of promoter CpG methylation in the epigenetic control of stem cell related genes during differentiation. Cell Cycle 8(6):916–924. CrossRefGoogle Scholar
  24. Declerck K, Remy S, Wohlfahrt-Veje C, Main KM, van Camp G, Schoeters G, vanden Berghe W, Andersen HR (2017) Interaction between prenatal pesticide exposure and a common polymorphism in the PON1 gene on DNA methylation in genes associated with cardio-metabolic disease risk—an exploratory study. Clin Epigenetics 9:35. CrossRefGoogle Scholar
  25. Desaulniers D, Xiao GH, Lian H, Feng YL, Zhu J, Nakai J, Bowers WJ (2009) Effects of mixtures of polychlorinated biphenyls, methylmercury, and organochlorine pesticides on hepatic DNA methylation in prepubertal female Sprague-Dawley rats. Int J Toxicol 28(4):294–307. CrossRefGoogle Scholar
  26. Ehrlich M (2009) DNA hypomethylation in cancer cells. Epigenomics 2:239–259. CrossRefGoogle Scholar
  27. El-Gazzar TF, El-dahdouh SS, El-Mahalawy II, Abd El-aty HE, Tayel SI (2016) Role of glutathione S-transferase P-1 (GSTP-1) gene polymorphism in COPD patients. Egyptian Journal of Chest Diseases and Tuberculosis 65:739–744. CrossRefGoogle Scholar
  28. Feinberg AP, Vogelstein B (1983) Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301(5895):89–92CrossRefGoogle Scholar
  29. Franco-Hernández C, Martínez-Glez V, Rey JA (2007) Biología molecular de los glioblastomas. Neurocirugía 18:373–382CrossRefGoogle Scholar
  30. Fujiwara-Igarashi A (2013) Simultaneous inactivation of the p16, p15, and p14 genes encoding cyclin-dependent kinase inhibitors in canine T-lymphoid tumor cells. Bull Nippon Vet Life Sci Univ 62:31–42. CrossRefGoogle Scholar
  31. Guerrero-Bosagna C, Settles M, Lucker B, Skinner MK (2010) Epigenetic transgenerational actions of vinclozolin on promoter regions of the sperm epigenome. PLoS One 5(9).
  32. Hernández-Ávila M, Romieu I, Parra S, Hernández-Avila J, Madrigal H, Willet W (1998) Validity and reproducibility of a food frequency questionnaire to assess dietary intake of women living in Mexico City. Salud Publica Mex 40(2):133–140CrossRefGoogle Scholar
  33. Hernández-Cortés D, Alvarado-Cruz I, Solís-Heredia MJ, Quintanilla-Vega B (2018) Epigenetic modulation of Nrf2 and Ogg1 gene expression in testicular germ cells by methyl parathion exposure. Toxicol Appl Pharmacol 346:19–27. CrossRefGoogle Scholar
  34. Hoar-Zahm S, Ward MH (1998) Pesticides and childhood cancer. Environ Health Perspect 106(3):893–908. CrossRefGoogle Scholar
  35. Howard TD, Hsu FC, Chen H, Quandt SA, Talton JW, Summers P, Arcury TA (2016) Changes in DNA methylation over the growing season differ between North Carolina farmworkers and non-farmworkers. Int Arch Occup Environ Health 89(7):1103–1110. CrossRefGoogle Scholar
  36. Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, He C, Zhang Y (2011) Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333(6047):1300–1303. CrossRefGoogle Scholar
  37. Itoh H, Iwasaki M, Kasuga Y, Yokoyama S, Onuma H, Nishimura H, Kusama R, Yoshida T, Yokoyama K, Tsugane S (2014) Association between serum organochlorines and global methylation level of leukocyte DNA among Japanese women: a cross-sectional study. Sci Total Environ 490:603–609. CrossRefGoogle Scholar
  38. Karami S, Andreotti G, Liao ML et al (2015) LINE1 methylation levels in pre-diagnostic leukocyte DNA and future renal cell carcinoma risk. Epigenetics 10(4):282–292. CrossRefGoogle Scholar
  39. Kim EH, Park AK, Dong SM, Ahn JH, Park WY (2010) Global analysis of CpG methylation reveals epigenetic control of the radiosensitivity in lung cancer cell lines. Oncogene 29(33):4725–4731. CrossRefGoogle Scholar
  40. Kwiatkowska M, Reszka E, Woźniak K, Jabłońska E, Michałowicz J, Bukowska B (2017) DNA damage and methylation induced by glyphosate in human peripheral blood mononuclear cells (in vitro study). Food Chem Toxicol 105:93–98. CrossRefGoogle Scholar
  41. Lee JE, Park JH, Shin IC, Koh HC (2012) Reactive oxygen species regulated mitochondria-mediated apoptosis in PC12 cells exposed to chlorpyrifos. Toxicol Appl Pharmacol 263(2):148–162. CrossRefGoogle Scholar
  42. Lee MH, Cho ER, Lim JE, Jee SH (2017) Association between serum persistent organic pollutants and DNA methylation in Korean adults. Environ Res 158:333–341. CrossRefGoogle Scholar
  43. Li J, Poi MJ, Tsai MD (2011) The regulatory mechanisms of tumor suppressor P16INK4A and relevance to cancer. Biochemistry 50(25):5566–5582. CrossRefGoogle Scholar
  44. Lim DH, Maher ER (2010) DNA methylation: a form of epigenetic control of gene expression. Obstet Gynaecol 12:37–42. CrossRefGoogle Scholar
  45. Manikkam M, Muksitul Haque M, Guerrero-Bosagna C, Nilsson EE, Skinner MK (2014) Pesticide methoxychlor promotes the epigenetic transgenerational inheritance of adult-onset disease through the female germline. PLoS One 9(7):e102091. CrossRefGoogle Scholar
  46. Maroni M, Colosio C, Ferioli A, Fait A (2000) Biological monitoring of pesticide exposure: a review. Introduction Toxicol 143(1):1–118Google Scholar
  47. McHugh D, Gil J (2017) Senescence and aging: causes, consequences, and therapeutic avenues. J Cell Biol.
  48. Mignone F, Gissi C, Liuni S, Pesole G (2002) Untranslated regions of mRNAs. Genome Biol 3(3) REVIEWS0004Google Scholar
  49. Moore LD, Le T, Fan G (2013) DNA methylation and its basic function. Neuropsychopharmacology 38(1):23–38. CrossRefGoogle Scholar
  50. Moosavi A, Motevalizadeh Ardekani A (2016) Role of epigenetics in biology and human diseases. Iran Biomed J 5:246–258. CrossRefGoogle Scholar
  51. Mostafalou S, Abdollahi M (2013) Pesticides and human chronic diseases: evidences, mechanisms, and perspectives. Toxicol Appl Pharmacol 268:157–177. CrossRefGoogle Scholar
  52. Mostafalou S, Abdollahi M (2017) Pesticides: an update of human exposure and toxicity. Arch Toxicol 91:549–599. CrossRefGoogle Scholar
  53. Muhonen P, Holthofer H (2009) Epigenetic and microRNA-mediated regulation in diabetes. Nephrol Dial Transplant 4:1088–1096. CrossRefGoogle Scholar
  54. Mund C, Brueckner B, Lyko F (2006) Reactivation of epigenetically silenced genes by DNA methyltransferase inhibitors: basic concepts and clinical applications. Epigenetics 1(1):8–14. CrossRefGoogle Scholar
  55. Nicolopoulou-Stamati P, Maipas S, Kotampasi C, Stamatis P, Hens L (2016) Chemical pesticides and human health: the urgent need for a new concept in agriculture. Front Public Health 4:148CrossRefGoogle Scholar
  56. O’Sullivan M, Scott SD, McCarthy N et al (2003) Differential cyclin E expression in human in-stent stenosis smooth muscle cells identifies targets for selective anti-restenosis therapy. Cardiovasc Res 60(3):673–683. CrossRefGoogle Scholar
  57. Ogawa M, Sakashita K, Zhaoa XY, Hayakawa A, Kubota T, Koike K (2007) Analysis of histone modification around the CpG island región of the p15 gene in acute myeloblastic leukemia. Leuk Res 31:611–621. CrossRefGoogle Scholar
  58. Qin Y, Liu JY, Li B, Sun ZL, Sun ZF (2004) Association of low p16INK4a and p15INK4b mRNAs expression with their CpG islands methylation with human hepatocellular carcinogénesis. World J Gastroenterol 10(9):1276–1280. CrossRefGoogle Scholar
  59. Ramírez-Jiménez R, Mejía-Saucedo R, Calderón-Hernández J, Montero-Montoya R, Yáñez-Estrada L (2014) Concentraciones urinarias de metabolitos de plaguicidas organofosforados en niños y adolescentes de una zona agrícola de México. Revista Iberoamericana de Ciencias 1(4):87–94Google Scholar
  60. Rivenbark AG, Stolzenburg S, Beltran AS, Yuan X, Rots MG, Strahl BD, Blancafort P (2012) Epigenetic reprogramming of cancer cells via targeted DNA methylation. Epigenetics 7(4):350–360. CrossRefGoogle Scholar
  61. Rodrigues EF, Santos-Rebouças CB, Gonçalves Pimentel MM, Mencalha AL, Dobbin J, da Costa ES, Fernandez CDS, Bouzas LF, Abdelhay E, de Souza Fernandez T (2010) Epigenetic alterations of p15(INK4B) and p16(INK4A) genes in pediatric primary myelodysplastic syndrome. Leuk Lymphoma 51(10):1887–1894. CrossRefGoogle Scholar
  62. Rodriguez-Menocal L, Pham SM, Mateu D et al (2009) Aging increases p16 INK4a expression in vascular smooth-muscle cells. Biosci Rep 30(1):11–18. CrossRefGoogle Scholar
  63. Rosas SL, Koch W, da Costa Carvalho MG et al (2001) Promoter hypermethylation patterns of p16, O6-methylguanine-DNA-methyltransferase, and death-associated protein kinase in tumors and saliva of head and neck cancer patients. Cancer Res 61(3):939–942Google Scholar
  64. Rusiecki JA, Baccarelli A, Bollati V, Tarantini L, Moore LE, Bonefeld-Jorgensen EC (2008) Global DNA hypomethylation is associated with high serum-persistent organic pollutants in Greenlandic Inuit. Environ Health Perspect 116(11):1547–1552. CrossRefGoogle Scholar
  65. Rusiecki JA, Beane Freeman LE, Bonner MR, Alexander M, Chen L, Andreotti G, Barry KH, Moore LE, Byun HM, Kamel F, Alavanja M, Hoppin JA, Baccarelli A (2017) High pesticide exposure events and DNA methylation among pesticide applicators in the agricultural health study. Environ Mol Mutagen 58(1):19–29. CrossRefGoogle Scholar
  66. Sharma V, Jha AK, Kumar A, Bhatnagar A, Narayan G, Kaur J (2015) Curcumin-mediated reversal of p15 gene promoter methylation: implication in anti-neoplastic action against acute lymphoid leukaemia cell line. Folia Biol (Praha) 61:81–89Google Scholar
  67. Sherr CJ, Roberts JM (2004) Living with or without cyclins and cyclin-dependent kinases. Genes Dev 18(22):2699–2711. CrossRefGoogle Scholar
  68. Shima K, Nosho K, Baba Y, Cantor M, Meyerhardt JA, Giovannucci EL, Fuchs CS, Ogino S (2011) Prognostic significance of CDKN2A (p16) promoter methylation and loss of expression in 902 colorectal cancers: cohort study and literature review. Int J Cancer 128:1080–1094. CrossRefGoogle Scholar
  69. Sokoloff K, Fraser W, Arbuckle TE, Fisher M, Gaudreau E, LeBlanc A, Morisset AS, Bouchard MF (2016) Determinants of urinary concentrations of dialkyl phosphates among pregnant women in Canada—results from the MIREC study. Environ Int 94:133–140. CrossRefGoogle Scholar
  70. Stanganelli C, Arbelbide J, Fantl DB, Corrado C, Slavutsky I (2009) DNA methylation analysis of tumor suppressor genes in monoclonal gammopathy of undetermined significance. Ann Hematol 89(2):191–199. CrossRefGoogle Scholar
  71. Tadokoro H, Shigihara T, Ikeda T, Takase M, Suyama M (2007) Two distinct pathways of p16 gene inactivation in gallbladder cancer. World J Gastroenterol 13(47):6396–6403. CrossRefGoogle Scholar
  72. Teneng I, Montoya-Durango DE, Quertermous JL, Lacy ME, Ramos KS (2011) Reactivation of L1 retrotransposon by benzo(a)pyrene involves complex genetic and epigenetic regulation. Epigenetics 6(3):355–367. CrossRefGoogle Scholar
  73. Valcke M, Samuel O, Bouchard M, Dumas P, Belleville D, Tremblay C (2006) Biological monitoring of exposure to organophosphate pesticides in children living in peri-urban areas of the Province of Quebec, Canada. Int Arch Occup Environ Health 79(7):568–577. CrossRefGoogle Scholar
  74. van Bemmel D, Lenz P, Liao LM et al (2012) Correlation of LINE-1 methylation levels in patient-matched buffy coat, serum, buccal cell, and bladder tumor tissue DNA samples. Cancer Epidemiol Biomark Prev 7:1143–1148. CrossRefGoogle Scholar
  75. van der Plaat DA, de Jong K, de Vries M, van Diemen CC, Nedeljković I, Amin N, Kromhout H, Biobank-based Integrative Omics Study Consortium, Vermeulen R, Postma DS, van Duijn CM, Boezen HM, Vonk JM (2018) Occupational exposure to pesticides is associated with differential DNA methylation. Occup Environ Med 75(6):427–435. CrossRefGoogle Scholar
  76. Van Maele-Fabry G, Lantin AC, Hoet P, Lison D (2011) Residential exposure to pesticides and childhood leukaemia: a systematic review and meta-analysis. Environ Int 37:280–291. CrossRefGoogle Scholar
  77. Viswanathan M, Tsuchida N, Shanmugam G (2003) Promoter hypermethylation profile of tumor-associated genes p16, p15, hMLH1, MGMT and E-cadherin in oral squamous cell carcinoma. Int J Cancer 105:41–46. CrossRefGoogle Scholar
  78. Wegman-Ostrosky T, Candelaria M, Duenas-Gonzalez A (2007) Epigenetic and hematological malignancies. Cancerología 2:159–170Google Scholar
  79. Wiaderkiewicz R, Walter Z, Reimschussel W (1986) Sites of methylation of DNA bases by the action of organophosphorus insecticides in vitro. Acta Biochim Pol 33(2):73–85Google Scholar
  80. Wigle DT, Turner MC, Krewski D (2009) A systematic review and meta-analysis of childhood leukemia and parental occupational pesticide exposure. Environ Health Perspect 117(10):1505–1513. CrossRefGoogle Scholar
  81. Witcher M, Emerson BM (2009) Epigenetic silencing of the p16(INK4a) tumor suppressor is associated with loss of CTCF binding and a chromatin boundary. Mol Cell 34(3):271–284. CrossRefGoogle Scholar
  82. Wolffe AP, Matzke MA (1999) Epigenetics: regulation through repression. Science 286(5439):481–486CrossRefGoogle Scholar
  83. Yeh KT, Shih MC, Lin TH et al (2002) The correlation between CpG methylation on promoter and protein expression of E-cadherin in oral squamous cell carcinoma. Anticancer 22:3971–3975Google Scholar
  84. Yoon KJ, Vissers C, Ming GL, Song H (2018) Epigenetics and epitranscriptomics in temporal patterning of cortical neural progenitor competence. J Cell Biol 217:1–14CrossRefGoogle Scholar
  85. Zhang X, Wallace AD, Du P et al (2012a) Genome-wide study of DNA methylation alterations in response to Diazinon exposure in vitro. Environ Toxicol Pharmacol 34(3):959–968. CrossRefGoogle Scholar
  86. Zhang X, Wallace AD, Du P et al (2012b) DNA methylation alterations in response to pesticide exposure in vitro. Environ Mol Mutagen 53(7):542–549. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • José Francisco Herrera-Moreno
    • 1
    • 2
  • Irma Martha Medina-Díaz
    • 1
  • Yael Yvette Bernal-Hernández
    • 1
  • Kenneth S. Ramos
    • 3
  • Isabel Alvarado-Cruz
    • 4
  • Betzabet Quintanilla-Vega
    • 4
  • Cyndia Azucena González-Arias
    • 1
  • Briscia Socorro Barrón-Vivanco
    • 1
  • Aurora Elizabeth Rojas-García
    • 1
    Email author
  1. 1.Laboratorio de Contaminación y Toxicología Ambiental, Secretaría de Investigación y PosgradoUniversidad Autónoma de NayaritTepicMexico
  2. 2.Posgrado en Ciencias Biológico AgropecuariasUnidad Académica de AgriculturaXaliscoMexico
  3. 3.Department of Medicine, Division of Clinical Support and Data AnalyticsUniversity of Arizona College of Medicine—PhoenixPhoenixUSA
  4. 4.Departamento de ToxicologíaCentro de Investigación y de Estudios Avanzados del IPNCiudad de MéxicoMexico

Personalised recommendations