Skip to main content

Advertisement

SpringerLink
Log in

Differential metabolism of inorganic arsenic in mice from genetically diverse Collaborative Cross strains

  • Inorganic Compounds
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Mice have been frequently used to study the adverse effects of inorganic arsenic (iAs) exposure in laboratory settings. Like humans, mice metabolize iAs to monomethyl-As (MAs) and dimethyl-As (DMAs) metabolites. However, mice metabolize iAs more efficiently than humans, which may explain why some of the effects of iAs reported in humans have been difficult to reproduce in mice. In the present study, we searched for mouse strains in which iAs metabolism resembles that in humans. We examined iAs metabolism in male mice from 12 genetically diverse Collaborative Cross (CC) strains that were exposed to arsenite in drinking water (0.1 or 50 ppm) for 2 weeks. Concentrations of iAs and its metabolites were measured in urine and livers. Significant differences in total As concentration and in proportions of total As represented by iAs, MAs, and DMAs were observed between the strains. These differences were more pronounced in livers, particularly in mice exposed to 50 ppm iAs. In livers, large variations among the strains were found in percentage of iAs (15–48%), MAs (11–29%), and DMAs (29–66%). In contrast, DMAs represented 96–99% of total As in urine in all strains regardless of exposure. Notably, the percentages of As species in urine did not correlate with total As concentration in liver, suggesting that the urinary profiles were not representative of the internal exposure. In livers of mice exposed to 50 ppm, but not to 0.1 ppm iAs, As3mt expression correlated with percent of iAs and DMAs. No correlations were found between As3mt expression and the proportions of As species in urine regardless of exposure level. Although we did not find yet a CC strain in which proportions of As species in urine would match those reported in humans (typically 10–30% iAs, 10–20% MAs, 60–70% DMAs), CC strains characterized by low %DMAs in livers after exposure to 50 ppm iAs (suggesting inefficient iAs methylation) could be better models for studies aiming to reproduce effects of iAs described in humans.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Agusa T, Iwata H, Fujihara J, Kunito T, Takeshita H, Minh TB, Trang PT, Viet PH, Tanabe S (2010) Genetic polymorphisms in glutathione S-transferase (GST) superfamily and arsenic metabolism in residents of the Red River Delta, Vietnam. Toxicol Appl Pharmacol 242(3):352–362

    Article  CAS  PubMed  Google Scholar 

  • Agusa T, Fujihara J, Takeshita H, Iwata H (2011) Individual variations in inorganic arsenic metabolism associated with AS3MT genetic polymorphisms. Int J Mol Sci 12(4):2351–2382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Agusa T, Kunito T, Tue NM, Lan VT, Fujihara J, Takeshita H, Minh TB, Trang PT, Takahashi S, Viet PH, Tanabe S, Iwata H (2012) Individual variations in arsenic metabolism in Vietnamese: the association with arsenic exposure and GSTP1 genetic polymorphism. Metallomics 4(1):91–100

    Article  CAS  PubMed  Google Scholar 

  • Antonelli R, Shao K, Thomas DJ, Sams R 2nd, Cowden J (2014) AS3MT, GSTO, and PNP polymorphisms: impact on arsenic methylation and implications for disease susceptibility. Environ Res 132:156–167

    Article  CAS  PubMed  Google Scholar 

  • ATSDR (2007) Toxicological Profile for Arsenic 2007. http://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=22&tid=3. Accessed 4 Sept 2019

  • Aylor DL, Valdar W, Foulds-Mathes W, Buus RJ, Verdugo RA, Baric RS, Ferris MT, Frelinger JA, Heise M, Frieman MB, Gralinski LE, Bell TA, Didion JD, Hua K, Nehrenberg DL, Powell CL, Steigerwalt J, Xie Y, Kelada SN, Collins FS, Yang IV, Schwartz DA, Branstetter LA, Chesler EJ, Miller DR, Spence J, Liu EY, McMillan L, Sarkar A, Wang J, Wang W, Zhang Q, Broman KW, Korstanje R, Durrant C, Mott R, Iraqi FA, Pomp D, Threadgill D, de Villena FP, Churchill GA (2011) Genetic analysis of complex traits in the emerging Collaborative Cross. Genome Res 21(8):1213–1222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beebe-Dimmer JL, Iyer PT, Nriagu JO, Keele GR, Mehta S, Meliker JR, Lange EM, Schwartz AG, Zuhlke KA, Schottenfeld D, Cooney KA (2012) Genetic variation in glutathione S-transferase omega-1, arsenic methyltransferase and methylene-tetrahydrofolate reductase, arsenic exposure and bladder cancer: a case–control study. Environ Health 11:43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caceres DD, Werlinger F, Orellana M, Jara M, Rocha R, Alvarado SA, Luis Q (2010) Polymorphism of glutathione S-transferase (GST) variants and its effect on distribution of urinary arsenic species in people exposed to low inorganic arsenic in tap water: an exploratory study. Arch Environ Occup Health 65(3):140–147

    Article  CAS  PubMed  Google Scholar 

  • Chen JW, Chen HY, Li WF, Liou SH, Chen CJ, Wu JH, Wang SL (2011) The association between total urinary arsenic concentration and renal dysfunction in a community-based population from central Taiwan. Chemosphere 84(1):17–24

    Article  CAS  PubMed  Google Scholar 

  • Chen JW, Wang SL, Wang YH, Sun CW, Huang YL, Chen CJ, Li WF (2012) Arsenic methylation, GSTO1 polymorphisms, and metabolic syndrome in an arseniasis endemic area of southwestern Taiwan. Chemosphere 88(4):432–438

    Article  CAS  PubMed  Google Scholar 

  • Chen X, Guo X, He P, Nie J, Yan X, Zhu J, Zhang L, Mao G, Wu H, Liu Z, Aga D, Xu P, Smith M, Ren X (2017) Interactive influence of N6AMT1 and As3MT genetic variations on arsenic metabolism in the population of Inner Mongolia, China. Toxicol Sci 155(1):124–134

    Article  CAS  PubMed  Google Scholar 

  • Chung CJ, Hsueh YM, Bai CH, Huang YK, Huang YL, Yang MH, Chen CJ (2009) Polymorphisms in arsenic metabolism genes, urinary arsenic methylation profile and cancer. Cancer Causes Control 20(9):1653–1661

    Article  PubMed  Google Scholar 

  • Chung CJ, Pu YS, Su CT, Chen HW, Huang YK, Shiue HS, Hsueh YM (2010) Polymorphisms in one-carbon metabolism pathway genes, urinary arsenic profile, and urothelial carcinoma. Cancer Causes Control 21(10):1605–1613

    Article  PubMed  Google Scholar 

  • Chung CJ, Pu YS, Su CT, Huang CY, Hsueh YM (2011) Gene polymorphisms of glutathione S-transferase omega 1 and 2, urinary arsenic methylation profile and urothelial carcinoma. Sci Total Environ 409(3):465–470

    Article  CAS  PubMed  Google Scholar 

  • Currier JM, Svoboda M, de Moraes DP, Matousek T, Dĕdina J, Stýblo M (2011) Direct analysis of methylated trivalent arsenicals in mouse liver by hydride generation-cryotrapping-atomic absorption spectrometry. Chem Res Toxicol 24(4):478–480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Currier JM, Douillet C, Drobná Z, Stýblo M (2016) Oxidation state specific analysis of arsenic species in tissues of wild-type and arsenic (+ 3 oxidation state) methyltransferase-knockout mice. J Environ Sci (China) 49:104–112

    Article  Google Scholar 

  • Das N, Giri A, Chakraborty S, Bhattacharjee P (2016) Association of single nucleotide polymorphism with arsenic-induced skin lesions and genetic damage in exposed population of West Bengal, India. Mutat Res 809:50–56

    Article  CAS  PubMed  Google Scholar 

  • de la Rosa R, Steinmaus C, Akers NK, Conde L, Ferreccio C, Kalman D, Zhang KR, Skibola CF, Smith AH, Zhang L, Smith MT (2017) Associations between arsenic (+ 3 oxidation state) methyltransferase (AS3MT) and N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) polymorphisms, arsenic metabolism, and cancer risk in a Chilean population. Environ Mol Mutagen 58(6):411–422

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Del Razo LM, Garcia-Vargas GG, Vargas H, Albores A, Gonsebatt ME, Montero R, Ostrosky-Wegman P, Kelsh M, Cebrian ME (1997) Altered profile of urinary arsenic metabolites in adults with chronic arsenicism. A pilot study. Arch Toxicol 71:211–217

    Article  PubMed  Google Scholar 

  • Douillet C, Huang MC, Saunders RJ, Dover EN, Zhang C, Styblo M (2017) Knockout of arsenic (+ 3 oxidation state) methyltransferase is associated with adverse metabolic phenotype in mice: the role of sex and arsenic exposure. Arch Toxicol 91(7):2617–2627

    Article  CAS  PubMed  Google Scholar 

  • Drobna Z, Naranmandura H, Kubachka KM, Edwards BC, Herbin-Davis K, Styblo M, Le XC, Creed JT, Maeda N, Hughes MF, Thomas DJ (2009) Disruption of the arsenic (+ 3 oxidation state) methyltransferase gene in the mouse alters the phenotype for methylation of arsenic and affects distribution and retention of orally administered arsenate. Chem Res Toxicol 22(10):1713–1720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Drobna Z, Del Razo LM, Garcia-Vargas GG, Sanchez-Pena LC, Barrera-Hernandez A, Styblo M, Loomis D (2013) Environmental exposure to arsenic, AS3MT polymorphism and prevalence of diabetes in Mexico. J Expo Sci Environ Epidemiol 23(2):151–155

    Article  CAS  PubMed  Google Scholar 

  • Engstrom KS, Vahter M, Fletcher T, Leonardi G, Goessler W, Gurzau E, Koppova K, Rudnai P, Kumar R, Broberg K (2015) Genetic variation in arsenic (+ 3 oxidation state) methyltransferase (AS3MT), arsenic metabolism and risk of basal cell carcinoma in a European population. Environ Mol Mutagen 56(1):60–69

    Article  PubMed  CAS  Google Scholar 

  • Faita F, Cori L, Bianchi F, Andreassi MG (2013) Arsenic-induced genotoxicity and genetic susceptibility to arsenic-related pathologies. Int J Environ Res Public Health 10(4):1527–1546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fu S, Wu J, Li Y, Liu Y, Gao Y, Yao F, Qiu C, Song L, Wu Y, Liao Y, Sun D (2014) Urinary arsenic metabolism in a Western Chinese population exposed to high-dose inorganic arsenic in drinking water: influence of ethnicity and genetic polymorphisms. Toxicol Appl Pharmacol 274(1):117–123

    Article  CAS  PubMed  Google Scholar 

  • Fujihara J, Fujii Y, Agusa T, Kunito T, Yasuda T, Moritani T, Takeshita H (2009) Ethnic differences in five intronic polymorphisms associated with arsenic metabolism within human arsenic (+ 3 oxidation state) methyltransferase (AS3MT) gene. Toxicol Appl Pharmacol 234(1):41–46

    Article  CAS  PubMed  Google Scholar 

  • Gribble MO, Voruganti VS, Cropp CD, Francesconi KA, Goessler W, Umans JG, Silbergeld EK, Laston SL, Haack K, Kao WH, Fallin MD, Maccluer JW, Cole SA, Navas-Acien A (2013) SLCO1B1 variants and urine arsenic metabolites in the Strong Heart Family Study. Toxicol Sci 136(1):19–25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harari F, Engstrom K, Concha G, Colque G, Vahter M, Broberg K (2013) N-6-adenine-specific DNA methyltransferase 1 (N6AMT1) polymorphisms and arsenic methylation in Andean women. Environ Health Perspect 121(7):797–803

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hernandez A, Marcos R (2008) Genetic variations associated with interindividual sensitivity in the response to arsenic exposure. Pharmacogenomics 9(8):1113–1132

    Article  CAS  PubMed  Google Scholar 

  • Hernández-Zavala A, Matoušek T, Drobná Z, Paul DS, Walton F, Adair BM, Jiří D, Thomas DJ, Stýblo M (2008) Speciation analysis of arsenic in biological matrices by automated hydride generation-cryotrapping-atomic absorption spectrometry with multiple microflame quartz tube atomizer (multiatomizer). J Anal At Spectrom 23:342–351

    Article  PubMed  PubMed Central  Google Scholar 

  • Hopenhayn-Rich C, Biggs ML, Kalman DA, Moore LE, Smith AH (1996a) Arsenic methylation patterns before and after changing from high to lower concentrations of arsenic in drinking water. Environ Health Perspect 104:1200–1207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hopenhayn-Rich C, Biggs ML, Smith AH, Kalman DA, Moore LE (1996b) Methylation study of a population environmentally exposed to arsenic in drinking water. Environ Health Perspect 104:620–628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang MC, Douillet C, Dover EN, Zhang C, Beck R, Tejan-Sie A, Krupenko SA, Stýblo M (2018a) Metabolic phenotype of wild-type and As3mt-knockout C57BL/6J mice exposed to inorganic arsenic: the role of dietary fat and folate intake. Environ Health Perspect 126(12):127003

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang MC, Douillet C, Dover EN, Stýblo M (2018b) Prenatal arsenic exposure and dietary folate and methylcobalamin supplementation alter the metabolic phenotype of C57BL/6J mice in a sex-specific manner. Arch Toxicol 92(6):1925–1937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hughes MF, Kenyon EM, Edwards BC, Mitchell CT, Thomas DJ (1999) Strain-dependent disposition of inorganic arsenic in the mouse. Toxicology 137(2):95–108

    Article  CAS  PubMed  Google Scholar 

  • Keane TM, Goodstadt L, Danecek P, White MA, Wong K, Yalcin B, Heger A, Agam A, Slater G, Goodson M, Furlotte NA, Eskin E, Nellåker C, Whitley H, Cleak J, Janowitz D, Hernandez-Pliego P, Edwards A, Belgard TG, Oliver PL, McIntyre RE, Bhomra A, Nicod J, Gan X, Yuan W, van der Weyden L, Steward CA, Bala S, Stalker J, Mott R, Durbin R, Jackson IJ, Czechanski A, Guerra-Assunção JA, Donahue LR, Reinholdt LG, Payseur BA, Ponting CP, Birney E, Flint J, Adams DJ (2011) Mouse genomic variation and its effect on phenotypes and gene regulation. Nature 477(7364):289–294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lindberg AL, Kumar R, Goessler W, Thirumaran R, Gurzau E, Koppova K, Rudnai P, Leonardi G, Fletcher T, Vahter M (2007) Metabolism of low-dose inorganic arsenic in a central European population: influence of sex and genetic polymorphisms. Environ Health Perspect 115(7):1081–1086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lindberg AL, Ekström EC, Nermell B, Rahman M, Lönnerdal B, Persson LA, Vahter M (2008) Gender and age differences in the metabolism of inorganic arsenic in a highly exposed population in Bangladesh. Environ Res 106(1):110–120

    Article  CAS  PubMed  Google Scholar 

  • Mazumder DN (2005) Effect of chronic intake of arsenic-contaminated water on liver. Toxicol Appl Pharmacol 206(2):169–175

    Article  PubMed  CAS  Google Scholar 

  • Naujokas MF, Anderson B, Ahsan H, Aposhian HV, Graziano JH, Thompson C, Suk WA (2013) The broad scope of health effects from chronic arsenic exposure: update on a worldwide public health problem. Environ Health Perspect 121(3):295–302

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paul DS, Hernández-Zavala A, Walton FS, Adair BM, Dedina J, Matousek T, Stýblo M (2007) Examination of the effects of arsenic on glucose homeostasis in cell culture and animal studies: development of a mouse model for arsenic-induced diabetes. Toxicol Appl Pharmacol 222(3):305–314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paul DS, Walton FS, Saunders RJ, Styblo M (2011) Characterization of the impaired glucose homeostasis produced in C57BL/6 mice by chronic exposure to arsenic and high-fat diet. Environ Health Perspect 119(8):1104–1109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paul S, Majumdar S, Giri AK (2015) Genetic susceptibility to arsenic-induced skin lesions and health effects: a review. Genes Environ. 37:23

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pierce BL, Kibriya MG, Tong L, Jasmine F, Argos M, Roy S, Paul-Brutus R, Rahaman R, Rakibuz-Zaman M, Parvez F, Ahmed A, Quasem I, Hore SK, Alam S, Islam T, Slavkovich V, Gamble MV, Yunus M, Rahman M, Baron JA, Graziano JH, Ahsan H (2012) Genome-wide association study identifies chromosome 10q24.32 variants associated with arsenic metabolism and toxicity phenotypes in Bangladesh. PLoS Genet 8(2):e1002522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rahbar MH, Samms-Vaughan M, Ma J, Bressler J, Loveland KA, Ardjomand-Hessabi M, Dickerson AS, Grove ML, Shakespeare-Pellington S, Beecher C, McLaughlin W, Boerwinkle E (2014) Role of metabolic genes in blood arsenic concentrations of Jamaican children with and without autism spectrum disorder. Int J Environ Res Public Health 11(8):7874–7895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Recio-Vega R, Gonzalez-Cortes T, Olivas-Calderon E, Clark Lantz R, Jay Gandolfi A, Michel-Ramirez G (2016) Association between polymorphisms in arsenic metabolism genes and urinary arsenic methylation profiles in girls and boys chronically exposed to arsenic. Environ Mol Mutagen 57(7):516–525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodrigues EG, Kile M, Hoffman E, Quamruzzaman Q, Rahman M, Mahiuddin G, Hsueh Y, Christiani DC (2012) GSTO and AS3MT genetic polymorphisms and differences in urinary arsenic concentrations among residents in Bangladesh. Biomarkers 17(3):240–247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schlawicke Engstrom K, Nermell B, Concha G, Stromberg U, Vahter M, Broberg K (2009) Arsenic metabolism is influenced by polymorphisms in genes involved in one-carbon metabolism and reduction reactions. Mutat Res 667(1–2):4–14

    Article  CAS  Google Scholar 

  • Spratlen MJ, Grau-Perez M, Best LG, Yracheta J, Lazo M, Vaidya D, Balakrishnan P, Gamble MV, Francesconi KA, Goessler W, Cole SA, Umans JG, Howard BV, Navas-Acien A (2018) The association of arsenic exposure and arsenic metabolism with the metabolic syndrome and its individual components: prospective evidence from the strong heart family study. Am J Epidemiol 187(8):1598–1612

    Article  PubMed  PubMed Central  Google Scholar 

  • Stanton BA, Caldwell K, Congdon CB, Disney J, Donahue M, Ferguson E, Flemings E, Golden M, Guerinot ML, Highman J, James K, Kim C, Lantz RC, Marvinney RG, Mayer G, Miller D, Navas-Acien A, Nordstrom DK, Postema S, Rardin L, Rosen B, SenGupta A, Shaw J, Stanton E, Susca P (2015) MDI biological laboratory arsenic summit: approaches to limiting human exposure to arsenic. Curr Environ Health Rep 2(3):329–337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steinmaus C, Bates MN, Yuan Y, Kalman D, Atallah R, Rey OA, Biggs ML, Hopenhayn C, Moore LE, Hoang BK, Smith AH (2006) Arsenic methylation and bladder cancer risk in case–control studies in Argentina and the United States. J Occup Environ Med 48(5):478–488

    Article  CAS  PubMed  Google Scholar 

  • Steinmaus C, Moore LE, Shipp M, Kalman D, Rey OA, Biggs ML, Hopenhayn C, Bates MN, Zheng S, Wiencke JK, Smith AH (2007) Genetic polymorphisms in MTHFR 677 and 1298, GSTM1 and T1, and metabolism of arsenic. J Toxicol Environ Health A 70(2):159–170

    Article  CAS  PubMed  Google Scholar 

  • Thomas DJ, Li J, Waters SB, Xing W, Adair BM, Drobna Z, Devesa V, Styblo M (2007) Arsenic (+ 3 oxidation state) methyltransferase and the methylation of arsenicals. Exp Biol Med 232(1):3–13

    Article  CAS  Google Scholar 

  • Tseng CH (2007) Arsenic methylation, urinary arsenic metabolites and human diseases: current perspective. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 25(1):1–22

    Article  CAS  PubMed  Google Scholar 

  • Vahter M (1999) Methylation of inorganic arsenic in different mammalian species and population groups. Sci Prog 82(Pt 1):69–88

    Article  CAS  PubMed  Google Scholar 

  • Vahter M (2000) Genetic polymorphism in the biotransformation of inorganic arsenic and its role in toxicity. Toxicol Lett 112–113:209–217

    Article  PubMed  Google Scholar 

  • Yang J, Yan L, Zhang M, Wang Y, Wang C, Xiang Q (2015) Associations between the polymorphisms of GSTT1, GSTM1 and methylation of arsenic in the residents exposed to low-level arsenic in drinking water in China. J Hum Genet 60(7):387–394

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by a UNC Systems Genetics Core Facility CC Pilot Program grant and by the following grants from NIEHS: R01ES022697 to M.S., R01ES028721 to M.S. and R.F., R01ES029925 to R.F., F.P.M.D.V., and M.S., and by the UNC Nutrition Obesity Research Center grant DK056350 from NIDDK.

Author information

Authors and Affiliations

  1. Department of Nutrition, CB# 7461, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7461, USA

    Miroslav Stýblo & Christelle Douillet

  2. Department of Environmental Sciences and Engineering, CB#7431, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7431, USA

    Jacqueline Bangma, Lauren A. Eaves & Rebecca Fry

  3. Department of Genetics, Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA

    Fernando Pardo-Manuel de Villena

Authors
  1. Miroslav Stýblo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christelle Douillet
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jacqueline Bangma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lauren A. Eaves
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fernando Pardo-Manuel de Villena
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rebecca Fry
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Miroslav Stýblo or Rebecca Fry.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 3106 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stýblo, M., Douillet, C., Bangma, J. et al. Differential metabolism of inorganic arsenic in mice from genetically diverse Collaborative Cross strains. Arch Toxicol 93, 2811–2822 (2019). https://doi.org/10.1007/s00204-019-02559-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-019-02559-7

Keywords

Search

Navigation