Cadmium Exposure and Blood Telomere Length in Female University Students in Japan

  • Yuki Mizuno
  • Shoko Konishi
  • Hideki Imai
  • Eiji Fujimori
  • Nobuhiko Kojima
  • Jun YoshinagaEmail author


Cadmium is a toxic metal found ubiquitously throughout the world. Our study evaluated whether cadmium exposure was associated with telomere length in 73 female university students. Determination of telomere length was performed by quantitative polymerase chain reaction using DNA in blood. Urinary cadmium concentration was measured by inductively coupled plasma mass spectrometry. The students’ physiological attributes and lifestyle were surveyed by means of a self-administered questionnaire. The geometric mean of urinary cadmium concentration was 0.312 μg/g creatinine, which was lower than the levels previously reported for Japan. Urinary cadmium concentration was not significantly associated with telomere length, though the exposure level of the present subjects was similar to that of previous study subjects which found significantly negative associations. It is possible that other factors affected telomere length in this study population.


Cadmium Female university student Japan Blood telomere length 



Body mass index


Inductively coupled plasma mass spectrometry


Polymerase chain reaction

T/S ratio

Telomere/single copy gene ratio



We thank the subjects of this study for their cooperation, and Ms. Yoko Nakamura, Faculty of Life Sciences, Toyo University, for helping with the preparation of the collection of samples.


This work was funded by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (grant number 16H05254).

Compliance with Ethical Standards

Conflict of Interest

Shoko Konishi and Jun Yoshinaga have received research grants from the Japan Society for the Promotion of Science.

Yuki Mizuno, Eiji Fujimori, Nobuhiko Kojima and Hideki Imai declare that they have no conflict of interest.

Ethical Approval

This study was approved by the Ethics Committee of Toyo University, Tokyo Healthcare University, and the Faculty of Medicine at the University of Tokyo in Japan.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

12011_2019_1656_MOESM1_ESM.docx (16 kb)
Table S1 (DOCX 15 kb)


  1. 1.
    ATSDR (Agency for Toxic Substances and Disease Registry) (2012) Toxicological profile for cadmium. Available: 〈〉 (accessed 28.03.2018)
  2. 2.
    IPCS (International Programmeon Chemical Safety) (1992). Cadmium Environmental health criteria. Available: 〈http://wwwinchemorg/documents/ehc/ehc/ehc134htm〉 (accessed 28.03.2018)
  3. 3.
    FSCJ (Food Safety Commission of Japan) (2008) Pollutants assessment report for cadmiumGoogle Scholar
  4. 4.
    Zota AR, Needham BL, Blackburn EH, Lin J, Park SK, Rehkopf DH, Epel ES (2015) Associations of cadmium and lead exposure with leukocyte telomere length: findings from National Health and Nutrition Examination Survey, 1999-2002. Am J Epidemiol 181:127–136. CrossRefPubMedGoogle Scholar
  5. 5.
    Lin S, Huo X, Zhang Q, Fan X, Du L, Xu X, Qiu S, Zhang Y, Wang Y, Gu J (2013) Short placental telomere was associated with cadmium pollution in an electronic waste recycling town in China. PLoS One 8:e60815. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Fillman T, Shimizu-Furusawa H, Ng CFS, Parajuli RP, Watanabe C (2016) Association of cadmium and arsenic exposure with salivary telomere length in adolescents in Terai, Nepal. Environ Res 149:8–14. CrossRefPubMedGoogle Scholar
  7. 7.
    Kurenova EV, Mason JM (1997) Telomere functions. A Review Biochem 62:1242–1253Google Scholar
  8. 8.
    Blackburn EH (2005) Telomeres and telomerase: their mechanisms of action and the effects of altering their functions. FEBS Lett 579:859–862. CrossRefPubMedGoogle Scholar
  9. 9.
    Aubert G, Lansdorp PM (2008) Telomeres and aging. Physiol Rev 88:557–579. CrossRefPubMedGoogle Scholar
  10. 10.
    Zhou Y, Ning Z, Lee Y, Hambly BD, McLachlan CS (2016) Shortened leukocyte telomere length in type 2 diabetes mellitus: genetic polymorphisms in mitochondrial uncoupling proteins and telomeric pathways. Clin Transl Med 5:8. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Wang J, Dong X, Cao L, Sun Y, Qiu Y, Zhang Y, Cao R, Covasa M, Zhong L (2016) Association between telomere length and diabetes mellitus: a meta-analysis. J Int Med Res 44:1156–1173. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Ma H, Zhou Z, Wei S, Liu Z, Pooley KA, Dunning AM, Svenson U, Roos G, Hosgood HD, Shen M, Wei Q (2011) Shortened telomere length is associated with increased risk of cancer: a meta-analysis. PLoS One 6:e20466. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Zhu X, Han W, Xue W, Zou Y, Xie C, Du J, Jin G (2016) The association between telomere length and cancer risk in population studies. Sci Rep 6:1–10. CrossRefGoogle Scholar
  14. 14.
    Kume K, Kikukawa M, Hanyu H, Takata Y, Umahara T, Sakurai H, Kanetaka H, Ohyashiki K, Ohyashiki JH, Iwamoto T (2012) Telomere length shortening in patients with dementia with Lewy bodies. Eur J Neurol 19:905–910. CrossRefPubMedGoogle Scholar
  15. 15.
    Honig LS, Kang MS, Schupf N, Lee JH, Mayeux R (2012) Association of shorter leukocyte telomere repeat length with dementia and mortality. Arch Neurol 69:1332–1339CrossRefGoogle Scholar
  16. 16.
    O’Donnell CJ, Demissie S, Kimura M, Levy D, Gardner JP, White C, D’Agostino RB, Wolf PA, Polak J, Cupples LA, Aviv A (2008) Leukocyte telomere length and carotid artery intimai medial thickness: the Framingham heart study. Arterioscler Thromb Vasc Biol 28:1165–1171. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    D’Mello MJJ, Ross SA, Briel M, Anand SS, Gerstein H, Paré G (2015) Association between shortened leukocyte telomere length and cardiometabolic outcomes: systematic review and meta-analysis. Circ Cardiovasc Genet 8:82–90. CrossRefPubMedGoogle Scholar
  18. 18.
    Epel ES, Prather AA (2018) Stress, telomeres, and psychopathology: toward a deeper understanding of a triad of early aging. Annu Rev Clin Psychol 14:371–397. CrossRefPubMedGoogle Scholar
  19. 19.
    Zhu Y, Liu X, Ding X, Wang F, Geng X (2018) Telomere and its role in the aging pathways: telomere shortening, cell senescence and mitochondria dysfunction. Biogerontology 20(1):1–16. CrossRefPubMedGoogle Scholar
  20. 20.
    von Zglinicki T (2002) Oxidative stress shortens telomeres. Trends Biochem Sci 27:339–344. CrossRefGoogle Scholar
  21. 21.
    Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160:1–40. CrossRefPubMedGoogle Scholar
  22. 22.
    Huang J, Okuka M, Lu W, Tsibris JCM, McLean MP, Keefe DL, Liu L (2013) Telomere shortening and DNA damage of embryonic stem cells induced by cigarette smoke. Reprod Toxicol 35:89–95. CrossRefPubMedGoogle Scholar
  23. 23.
    Ikeda M, Zhang ZW, Moon CS, Shimbo S, Watanabe T, Nakatsuka H, Matsuda-Inoguchi N, Higashikawa K (2000) Possible effects of environmental cadmium exposure on kidney function in the Japanese general population. Int Arch Occup Environ Health 73:15–25. CrossRefPubMedGoogle Scholar
  24. 24.
    Ezaki T, Tsukahara T, Moriguchi J, Furuki K, Fukui Y, Ukai H, Okamoto S, Sakurai H, Honda S, Ikeda M (2003) No clear-cut evidence for cadmium-induced renal tubular dysfunction among over 10,000 women in the Japanese general population: a nationwide large-scale survey. Int Arch Occup Environ Health 76:186–196. CrossRefPubMedGoogle Scholar
  25. 25.
    Rivai IF, Koyama H, Suzuki S (1990) Cadmium content in rice and its daily intake in various countries. Bull Environ Contam Toxicol 44:910–916. CrossRefPubMedGoogle Scholar
  26. 26.
    Tsukahara T, Ezaki T, Moriguchi J, Furuki K, Shimbo S, Matsuda-Inoguchi N, Ikeda M (2003) Rice as the most influential source of cadmium intake among general Japanese population. Sci Total Environ 305:41–51. CrossRefPubMedGoogle Scholar
  27. 27.
    MizunoY FE, Yoshinaga J (2017) Determination of urinary cadmium by ICP-MS: correction and removal of spectral interference from MoO. Biomed Res Trace Elem 28(4):154–161Google Scholar
  28. 28.
    Bonsnes RW, Taussky HH (1945) On colorimetric determination of creatinine by the Jaffe reaction. J Biol Chem 158:581–591Google Scholar
  29. 29.
    Cawthon RM (2002) Telomere measurement by quantitative PCR. Nucleic Acids Res 30:e47. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Lin J, Epel E, Cheon J, Kroenke C, Sinclair E, Bigos M, Wolkowitz O, Mellon S, Blackburn E (2010) Analyses and comparisons of telomerase activity and telomere length in human T and B cells: insights for epidemiology of telomere maintenance. J Immunol Methods 352:71–80. CrossRefPubMedGoogle Scholar
  31. 31.
    Tucker LA (2017) Caffeine consumption and telomere length in men and women of the National Health and Nutrition Examination Survey (NHANES). Nutr Metab (Lond) 14:10. CrossRefGoogle Scholar
  32. 32.
    Wang H, Kim H, Baik I (2017) Associations of alcohol consumption and alcohol flush reaction with leukocyte telomere length in Korean adults. Nutr Res Pract 11:334–339. CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Wulaningsih W, Serrano FEC, Utarini A, Matsuguchi T, Watkins J (2016) Smoking, second-hand smoke exposure and smoking cessation in relation to leukocyte telomere length and mortality. Oncotarget 7:60419–60431. CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Hunt SC, Chen W, Gardner JP, Kimura M, Srinivasan SR, Eckfeldt JH, Berenson GS, Aviv A (2008) Leukocyte telomeres are longer in African Americans than in whites: the National Heart, Lung, and Blood Institute family heart study and the Bogalusa heart study. Aging Cell 7:451–458. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Tsuda M, Hasunuma R, Kawanishi Y, Okazaki I (1995) Urinary concentrations of heavy metals in healthy Japanese under 20 years of age: a comparison between concentrations expressed in terms of creatinine and of selenium. Tokai J Exp Clin Med 20:53–64PubMedGoogle Scholar
  36. 36.
    Ministry of Agriculture, Forestry and fisheries, 1981-2015. Annual change of Cd intake Available: 〈〉 (accessed 28.03.2018)
  37. 37.
    Ministry of Agriculture, Forestry and fisheries, 2003-2016. The tables of supply and demand of food Available: 〈〉 (accessed 28.03.2018)
  38. 38.
    Ministry of Agriculture, Forestry and fisheries, 2016. The results of survey of cadmium in food Available: 〈〉 (accessed 28.03.2018)
  39. 39.
    Houben JMJ, Moonen HJJ, van Schooten FJ, Hageman GJ (2008) Telomere length assessment: biomarker of chronic oxidative stress? Free Radic Biol Med 44:235–246. CrossRefPubMedGoogle Scholar
  40. 40.
    Waisberg M, Joseph P, Hale B, Beyersmann D (2003) Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicology 192:95–117. CrossRefPubMedGoogle Scholar
  41. 41.
    Patra RC, Rautray AK, Swarup D (2011) Oxidative stress in lead and cadmium toxicity and its amelioration. Vet Med Int 2011:1–9. CrossRefGoogle Scholar
  42. 42.
    Jeng HA, Pan CH, Diawara N, Chang-Chien GP, Lin WY, Huang CT, Ho CK, Wu MT (2011) Polycyclic aromatic hydrocarbon-induced oxidative stress and lipid peroxidation in relation to immunological alteration. Occup Environ Med 68:653–658. CrossRefPubMedGoogle Scholar
  43. 43.
    Flora SJS (2011) Arsenic-induced oxidative stress and its reversibility. Free Radic Biol Med 51:257–281. CrossRefPubMedGoogle Scholar
  44. 44.
    Ling X, Zhang G, Chen Q, Yang H, Sun L, Zhou N, Wang Z, Zou P, Wang X, Cui Z, Liu J, Ao L, Cao J (2016) Shorter sperm telomere length in association with exposure to polycyclic aromatic hydrocarbons: results from the MARHCS cohort study in Chongqing, China and in vivo animal experiments. Environ Int 95:79–85. CrossRefPubMedGoogle Scholar
  45. 45.
    Pawlas N, Płachetka A, Kozłowska A, Broberg K, Kasperczyk S (2015) Telomere length in children environmentally exposed to low-to-moderate levels of lead. Toxicol Appl Pharmacol 287:111–118. CrossRefPubMedGoogle Scholar
  46. 46.
    Mannan T, Ahmed S, Akhtar E, Ahsan K, Haq A, Kippler M, Vahter M, Raqib R (2018) Associations of arsenic exposure with telomere length and naïve T cells in childhood– a birth cohort study. Toxicol Sci 164:539–549. CrossRefPubMedGoogle Scholar
  47. 47.
    Benetos A, Kark JD, Susser E, Kimura M, Sinnreich R, Chen W, Steenstrup T, Christensen K, Herbig U, Von Bornemann Hjelmborg J, Srinivasan SR, Berenson GS, Labat C, Aviv A (2013) Tracking and fixed ranking of leukocyte telomere length across the adult life course. Aging Cell 12:615–621CrossRefGoogle Scholar
  48. 48.
    Vacchi-Suzzi C, Kruse D, Harrington J, Levine K, Meliker JR (2016) Is urinary cadmium a biomarker of long-term exposure in humans? A review. Curr Environ Health Rep 3(4):450–458CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Yuki Mizuno
    • 1
  • Shoko Konishi
    • 1
    • 2
  • Hideki Imai
    • 3
  • Eiji Fujimori
    • 4
  • Nobuhiko Kojima
    • 5
  • Jun Yoshinaga
    • 5
    Email author
  1. 1.Department of Human Ecology, School of International Health, Graduate School of MedicineUniversity of TokyoTokyoJapan
  2. 2.Department of AnthropologyUniversity of WashingtonSeattleUSA
  3. 3.Department of NursingTokyo Healthcare UniversityTokyoJapan
  4. 4.National Environmental Research and Training InstituteTokorozawa CityJapan
  5. 5.Faculty of Life SciencesToyo UniversityItakura, OraJapan

Personalised recommendations