medlitГигиена и санитарияHygiene and Sanitation0016-99002412-0650Federal Scientific Center of Hygiene named after F.F. Erisman10.47470/0016-9900-2021-100-11-1298-1302medlit-1851Research ArticleПРОФИЛАКТИЧЕСКАЯ ТОКСИКОЛОГИЯ И ГИГИЕНИЧЕСКОЕ НОРМИРОВАНИЕPREVENTIVE TOXICOLOGY AND HYGIENIC STANDARTIZATIONАнализ экспрессии генов MT1 и ZIP1 в печени крыс при хроническом отравлении хлоридом кадмияAnalysis of MT1 and ZIP1 gene expression in the liver of rats with chronic poisoning with cadmium chloridehttps://orcid.org/0000-0002-1848-7959ЗиатдиноваМунира МунировнаZiatdinovaMunira M.

Мл. науч. сотр. отд. токсикологии и генетики с экспериментальной клиникой лабораторных животных ФБУН «Уфимский научно-исследовательский институт медицины труда и экологии человека», 450106, Уфа.

e-mail: munira.munirovna@yandex.ru 

Junior Researcher of the Department of Toxicology and Genetics with an experimental laboratory of laboratory animals, UfaResearch Institute of Occupational Health and Human Ecology, Ufa, 450106, Russian Federation.

e-mail: munira.munirovna@yandex.ru

munira.munirovna@yandex.ruhttps://orcid.org/0000-0001-6605-9994ВаловаЯ. В.ValovaYana V.noemail@neicon.ruhttps://orcid.org/0000-0002-7456-4787МухаммадиеваГ. Ф.MukhammadiyevaGuzel F.noemail@neicon.ruhttps://orcid.org/0000-0002-0037-6791ФазлыеваА. С.FazlievaAnna S.noemail@neicon.ruhttps://orcid.org/0000-0002-1962-2323КаримовД. Д.KarimovDenis D.noemail@neicon.ruhttps://orcid.org/0000-0002-2092-1021КудояровЭ. Р.KudoyarovEldar R.noemail@neicon.ruФБУН «Уфимский научно-исследовательский институт медицины труда и экологии человека»РоссияUfa Research Institute of Occupational Health and Human EcologyRussian Federation2021061220211001112981302Copyright © Зиатдинова М.М., Валова Я.В., Мухаммадиева Г.Ф., Фазлыева А.С., Каримов Д.Д., Кудояров Э.Р., 20212021Зиатдинова М.М., Валова Я.В., Мухаммадиева Г.Ф., Фазлыева А.С., Каримов Д.Д., Кудояров Э.Р.Ziatdinova M.M., Valova Y.V., Mukhammadiyeva G.F., Fazlieva A.S., Karimov D.D., Kudoyarov E.R.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rjhas.ru/jour/article/view/1851Введение

Введение. Кадмий — это токсичный тяжёлый металл, оказывающий разрушительное воздействие на большинство систем органов. После абсорбции кадмий транспортируется по всему организму, в большинстве своём связываясь с белками металлотионеинами. Считается, что механизмы кадмий-индуцированной трансформации возникают в результате нарушения цинкзависимых клеточных процессов. Это связано со структурным и физическим сходством между цинком и кадмием. Больше половины поступившего кадмия депонируется в печени и почках, оставшаяся часть распределяется по остальным органам и их системам.

Материалы и методы

Материалы и методы. Всего в эксперименте были использованы 40 белых аутбредных крыс обоих полов массой тела 170–230 г, сформированных в 4 опытные группы по 10 особей в каждой, в зависимости от дозы вводимого токсиканта. В качестве материалов исследования использовали образцы тканей печени, в гомогенате которых определяли количественное содержание Cd и Zn, а также уровень мРНК генов MT1 и ZIP1.

Результаты

Результаты. Было установлено, что наиболее выраженная активность гена МТ1 в тканях печени была достигнута при введении животным хлорида кадмия в дозе 0,1 мг/кг (2,69 ± 0,37; p = 0,017), в то время как кратность экспрессии гена ZIP1 показала максимальное значение уровня транскриптов при минимальной дозе токсина (2,7 ± 0,37; p = 0,007). Также было показано, что наибольшую концентрацию цинка в печёночной ткани наблюдали при введении хлорида кадмия в дозе 0,1 мг/кг (33,84 ± 0,53; р < 0,001), а концентрация кадмия увеличивалась наряду с повышением дозы токсиканта (0,0049 ± 0,0003; 0,0203 ± 0,0024; 0,664 ± 0,007; 0,76 ± 0,0089).

Заключение

Заключение. Таким образом, комплексное изучение экспрессии генов металлотионеинов и транспортёров цинка может быть использовано в качестве биомаркера отравления кадмием и его соединениями.

Участие авторов

Участие авторов:Зиатдинова М.М. — концепция и дизайн исследования, сбор и обработка материала, статистическая обработка, написание текста;Валова Я.В. — сбор и обработка материала, статистическая обработка;Мухаммадиева Г.Ф., Фазлыева А.С., Каримов Д.Д., Кудояров Э.Р. — сбор и обработка материала.Все соавторы — утверждение окончательного варианта статьи, ответственность за целостность всех частей статьи.

Конфликт интересов

Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов в связи с публикацией данной статьи.

Финансирование

Финансирование. Бюджетная тема в рамках отраслевой программы Роспотребнадзора.

Заключение биоэтической комиссии ФБУН «Уфимский НИИ медицины труда и экологии человека»: проведённые исследования выполнены в соответствии с Европейской конвенцией о защите позвоночных животных, используемых для экспериментов или в иных научных целях (ETS N 123), директивой Европейского парламента и Совета Европейского союза 2010/63/EC от 22.09.2010 г. о защите животных, использующихся в научных целях.

Поступила

Поступила: 20.05.2021 / Принята к печати: 28.09.2021 / Опубликована: 30.11.2021

Introduction

Introduction. Cadmium is a toxic heavy metal with devastating effects on most organ systems. After absorption, cadmium is transported throughout the body, primarily by binding to proteins by metallothioneins. It is believed that the mechanisms of cadmium-induced transformation arise due to the disruption of zinc-dependent cellular processes. This part is due to the structural and physical similarities between zinc and cadmium. More than half of the incoming cadmium is deposited in the liver and kidneys. The rest part is distributed throughout other organs and their systems.

Materials and methods

Materials and methods. In total, 40 white outbred rats of both sexes weighing 170–230 g were used in the experiment; they were formed into four experimental groups of 10 animals each, depending on the dose of the injected toxicant. Liver tissue samples were used as research materials, in the homogenate of which the quantitative content of Cd and Zn was determined, as well as the mRNA level of the MT1 and ZIP1 genes.

Results

Results. It was found that the most pronounced activity of the MT1 gene in liver tissues was achieved when animals were administered cadmium chloride at a dose of 0.1 mg/kg (2.69 ± 0.37; p = 0.017), while the multiplicity of expression of the ZIP1 gene showed the maximum value of the level of transcripts with the minimum dose of toxin (2.70 ± 0.37; p = 0.007). It was also revealed that the highest concentration of zinc in the liver tissue was observed with the introduction of cadmium chloride at a dose of 0.1 mg/kg (33.84 ± 0.53; p <0.001), and the concentration of cadmium increased along with an increase in the dose of the toxicant (0, 0049 ± 0.0003; 0.0203 ± 0.0024; 0.664 ± 0.007; 0.76 ± 0.0089).

Conclusion

Conclusion. Thus, a comprehensive study of the expression of genes for metallothioneins and zinc transporters can be used as a biomarker of poisoning with cadmium and its compounds.

Contribution

Contribution:Ziatdinova M.M. — the concept and design of the study, the collection and processing of material, statistical processing, writing text;Valova Ya.V. — collection and processing of the material;Mukhammadiyeva G.F., Fazlieva A.S., Karimov D.D., Kudoyarov E.R. — collection and processing of the material.All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version

Conflict of interest

Conflict of interest. The authors declare no conflict of interest.

Acknowledgement

Acknowledgement. The budget topic within the sectoral program of the Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing

Conclusion of the bioethical commission: the study was approved by the bioethical commission of the “Ufa Research Institute of Occupational Health and Human Ecology”, carried out per the European Convention for the Protection of Vertebrate Animals Used for Experiments or Other Scientific Purposes (ETS N 123), the directive of the European Parliament and the Council of the European Union 2010/63 / EU of 22.09.2010 on the protection of animals used for scientific purposes.

Received

Received: May 20, 2021 / Accepted: September 28, 2021 / Published: November 30, 2021

хроническая интоксикацияхлорид кадмияэкспрессияконцентрацияметаллотионеинытранспортёры цинкацинккадмийchronic intoxicationcadmium chlorideexpressionconcentrationmetallothioneinszinc transporterszinccadmiumReferencesHu X., Chandler J.D., Park S., Liu K., Fernandes J., Orr M., et al. Low-dose cadmium disrupts mitochondrial citric acid cycle and lipid metabolism in mouse lung. Free Radic. Biol. Med. 2019; 131: 209-17. https://doi.org/10.1016/j.freeradbiomed.2018.12.005Hu X., Chandler J.D., Park S., Liu K., Fernandes J., Orr M., et al. Low-dose cadmium disrupts mitochondrial citric acid cycle and lipid metabolism in mouse lung. Free Radic. Biol. Med. 2019; 131: 209-17. https://doi.org/10.1016/j.freeradbiomed.2018.12.005Garrett S.H., Clarke K., Sens D.A., Deng Y., Somji S., Zhang K.K. Short- and long-term gene expression variation and networking in human proximal tubule cells when exposed to cadmium. BMC Med. Genomics. 2013; 6(Suppl. 1): S2. https://doi.org/10.1186/1755-8794-6-s1-s2Garrett S.H., Clarke K., Sens D.A., Deng Y., Somji S., Zhang K.K. Short- and long-term gene expression variation and networking in human proximal tubule cells when exposed to cadmium. BMC Med. Genomics. 2013; 6(Suppl. 1): S2. https://doi.org/10.1186/1755-8794-6-s1-s2Genchi G., Sinicropi M.S., Lauria G., Carocci A., Catalano A. The Effects of Cadmium Toxicity. Int. J. Environ. Res. Public. Health. 2020; 17(11): 3782. https://doi.org/10.3390/ijerph17113782Genchi G., Sinicropi M.S., Lauria G., Carocci A., Catalano A. The Effects of Cadmium Toxicity. Int. J. Environ. Res. Public. Health. 2020; 17(11): 3782. https://doi.org/10.3390/ijerph17113782Marettová E., Maretta M., Legáth J. Toxic effects of cadmium on testis of birds and mammals: a review. Anim. Reprod. Sci. 2015; 155: 1-10. https://doi.org/10.1016/j.anireprosci.2015.01.007Marettová E., Maretta M., Legáth J. Toxic effects of cadmium on testis of birds and mammals: a review. Anim. Reprod. Sci. 2015; 155: 1-10. https://doi.org/10.1016/j.anireprosci.2015.01.007Massányi P., Uhrín V., Toman R., Pivko J., Lukáč N., Forgács Z., et al. Ultrastructural changes of ovaries in rabbits following cadmium administration. Acta Vet. Brno. 2005; 74(1): 29-35. https://doi.org/10.2754/avb200574010029Massányi P., Uhrín V., Toman R., Pivko J., Lukáč N., Forgács Z., et al. Ultrastructural changes of ovaries in rabbits following cadmium administration. Acta Vet. Brno. 2005; 74(1): 29-35. https://doi.org/10.2754/avb200574010029Kumar S., Sharma A. Cadmium toxicity: Effects on human reproduction and fertility. Rev. Environ. Health. 2019; 34(4): 327-38. https://doi.org/10.1515/reveh-2019-0016Kumar S., Sharma A. Cadmium toxicity: Effects on human reproduction and fertility. Rev. Environ. Health. 2019; 34(4): 327-38. https://doi.org/10.1515/reveh-2019-0016Jeong E.M., Moon C.H., Kim C.S., Lee S.H., Baik E.J., Moon C.K., et al. Cadmium stimulates the expression of ICAM-1 via NF-kappaB activation in cerebrovascular endothelial cells. Biochem. Biophys. Res. Commun. 2004; 320(3): 887-92. https://doi.org/10.1016/j.bbrc.2004.05.218Jeong E.M., Moon C.H., Kim C.S., Lee S.H., Baik E.J., Moon C.K., et al. Cadmium stimulates the expression of ICAM-1 via NF-kappaB activation in cerebrovascular endothelial cells. Biochem. Biophys. Res. Commun. 2004; 320(3): 887-92. https://doi.org/10.1016/j.bbrc.2004.05.218Shagirtha K., Muthumani M., Prabu S.M. Melatonin abrogates cadmium induced oxidative stress related neurotoxicity in rats. Eur. Rev. Med. Pharmacol. Sci. 2011; 15(9): 1039-50.Shagirtha K., Muthumani M., Prabu S.M. Melatonin abrogates cadmium induced oxidative stress related neurotoxicity in rats. Eur. Rev. Med. Pharmacol. Sci. 2011; 15(9): 1039-50.Turley A.E., Zagorski J.W., Kennedy R.C., Freeborn R.A., Bursley J.K., Edwards J.R., et al. Chronic low-level cadmium exposure in rats affects cytokine production by activated T cells. Toxicol. Res. (Camb.) 2019; 8(2): 227-37. https://doi.org/10.1039/c8tx00194dTurley A.E., Zagorski J.W., Kennedy R.C., Freeborn R.A., Bursley J.K., Edwards J.R., et al. Chronic low-level cadmium exposure in rats affects cytokine production by activated T cells. Toxicol. Res. (Camb.) 2019; 8(2): 227-37. https://doi.org/10.1039/c8tx00194dUnsal V., Dalkıran T., Çiçek M., Kölükçü E. The role of natural antioxidants against reactive oxygen species produced by cadmium toxicity: a review. Adv. Pharmaceut. Bull. 2020; 10(2): 184-202. https://doi.org/10.34172/apb.2020.023Unsal V., Dalkıran T., Çiçek M., Kölükçü E. The role of natural antioxidants against reactive oxygen species produced by cadmium toxicity: a review. Adv. Pharmaceut. Bull. 2020; 10(2): 184-202. https://doi.org/10.34172/apb.2020.023Iftode A., Drăghici G.A., Macașoi I., Marcovici I., Coricovac D.E., Dragoi R., et al. Exposure to cadmium and copper triggers cytotoxic effects and epigenetic changes in human colorectal carcinoma HT-29 cells. Exp. Ther. Med. 2021; 21(1): 100. https://doi.org/10.3892/etm.2020.9532Iftode A., Drăghici G.A., Macașoi I., Marcovici I., Coricovac D.E., Dragoi R., et al. Exposure to cadmium and copper triggers cytotoxic effects and epigenetic changes in human colorectal carcinoma HT-29 cells. Exp. Ther. Med. 2021; 21(1): 100. https://doi.org/10.3892/etm.2020.9532Wang M., Wang J., Sun H., Han S., Feng S., Shi L., et al. Time-dependent toxicity of cadmium telluride quantum dots on liver and kidneys in mice: histopathological changes with elevated free cadmium ions and hydroxyl radicals. Int. J. Nanomedicine. 2016; 11: 2319-28. https://doi.org/10.2147/IJN.S103489Wang M., Wang J., Sun H., Han S., Feng S., Shi L., et al. Time-dependent toxicity of cadmium telluride quantum dots on liver and kidneys in mice: histopathological changes with elevated free cadmium ions and hydroxyl radicals. Int. J. Nanomedicine. 2016; 11: 2319-28. https://doi.org/10.2147/IJN.S103489Martinez-Zamudio R., Ha HC Environmental epigenetics in metal exposure. Epigenetics. 2011; 6(7): 820-7. https://doi.org/10.4161/epi.6.7.16250Martinez-Zamudio R., Ha HC Environmental epigenetics in metal exposure. Epigenetics. 2011; 6(7): 820-7. https://doi.org/10.4161/epi.6.7.16250Buha A., Wallace D., Matovic V., Schweitzer A., Oluic B., Micic D., et al. Cadmium exposure as a putative risk factor for the development of pancreatic Cancer: three different lines of evidence. Biomed. Res. Int. 2017; 2017: 1981837. https://doi.org/10.1155/2017/1981837Buha A., Wallace D., Matovic V., Schweitzer A., Oluic B., Micic D., et al. Cadmium exposure as a putative risk factor for the development of pancreatic Cancer: three different lines of evidence. Biomed. Res. Int. 2017; 2017: 1981837. https://doi.org/10.1155/2017/1981837Luevano J., Damodaran C. A review of molecular events of cadmium-induced carcinogenesis. J. Environ. Pathol. Toxicol. Oncol. 2014; 33(3): 183-94. https://doi.org/10.1615/jenvironpatholtoxicoloncol.2014011075Luevano J., Damodaran C. A review of molecular events of cadmium-induced carcinogenesis. J. Environ. Pathol. Toxicol. Oncol. 2014; 33(3): 183-94. https://doi.org/10.1615/jenvironpatholtoxicoloncol.2014011075Eide D.J. The SLC39 family of metal ion transporters. Pflugers. Arch. 2004; 447(5): 796-800. https://doi.org/10.1016/j.mam.2012.05.011Eide D.J. The SLC39 family of metal ion transporters. Pflugers. Arch. 2004; 447(5): 796-800. https://doi.org/10.1016/j.mam.2012.05.011Wang P., Zhang J., He S., Xiao B., Peng X. SLC39A1 contribute to malignant progression and have clinical prognostic impact in gliomas. Cancer Cell Int. 2020; 20(1): 573. https://doi.org/10.1186/s12935-020-01675-0Wang P., Zhang J., He S., Xiao B., Peng X. SLC39A1 contribute to malignant progression and have clinical prognostic impact in gliomas. Cancer Cell Int. 2020; 20(1): 573. https://doi.org/10.1186/s12935-020-01675-0Kondo Y., Woo E.S., Michalska A.E., Choo K.H., Lazo J.S. Metallothionein null cells have increased sensitivity to anticancer drugs. Cancer Res. 1995; 55(10): 2021-3.Kondo Y., Woo E.S., Michalska A.E., Choo K.H., Lazo J.S. Metallothionein null cells have increased sensitivity to anticancer drugs. Cancer Res. 1995; 55(10): 2021-3.Janssen A.M., van Duijn W., Kubben F.J., Griffioen G., Lamers C.B., van Krieken J.H., et al. Prognostic significance of metallothionein in human gastrointestinal cancer. Clin. Cancer Res. 2002; 8(6): 1889-96.Janssen A.M., van Duijn W., Kubben F.J., Griffioen G., Lamers C.B., van Krieken J.H., et al. Prognostic significance of metallothionein in human gastrointestinal cancer. Clin. Cancer Res. 2002; 8(6): 1889-96.Smith P.J., Wiltshire M., Furon E., Beattie J.H., Errington R.J. Impact of overexpression of metallothionein-1 on cell cycle progression and zinc toxicity. Am. J. Physiol. Cell. Physiol. 2008; 295(5): C1399-408. https://doi.org/10.1152/ajpcell.00342.2008Smith P.J., Wiltshire M., Furon E., Beattie J.H., Errington R.J. Impact of overexpression of metallothionein-1 on cell cycle progression and zinc toxicity. Am. J. Physiol. Cell. Physiol. 2008; 295(5): C1399-408. https://doi.org/10.1152/ajpcell.00342.2008Thirumoorthy N., Manisenthil Kumar K.T., Shyam Sundar A., Panayappan L., Chatterjee M. Metallothionein: an overview. World J. Gastroenterol. 2007; 13(7): 993-6. https://doi.org/10.3748/wjg.v13.i7.993Thirumoorthy N., Manisenthil Kumar K.T., Shyam Sundar A., Panayappan L., Chatterjee M. Metallothionein: an overview. World J. Gastroenterol. 2007; 13(7): 993-6. https://doi.org/10.3748/wjg.v13.i7.993Hosohata K., Mise N., Kayama F., Iwanaga K. Augmentation of cadmium-induced oxidative cytotoxicity by pioglitazone in renal tubular epithelial cells. Toxicol. Ind. Health. 2019; 35(8): 530-6. https://doi.org/10.1177/0748233719869548Hosohata K., Mise N., Kayama F., Iwanaga K. Augmentation of cadmium-induced oxidative cytotoxicity by pioglitazone in renal tubular epithelial cells. Toxicol. Ind. Health. 2019; 35(8): 530-6. https://doi.org/10.1177/0748233719869548Saedi S., Jafarzadeh Shirazi M.R., Totonchi M., Zamiri M.J., Derakhshanfar A. Effect of prepubertal exposure to CdCl2 on the liver, hematological, and biochemical parameters in female rats; an experimental study. Biol. Trace. Elem. Res. 2020; 194(2): 472-81. https://doi.org/10.1007/s12011-019-01800-9Saedi S., Jafarzadeh Shirazi M.R., Totonchi M., Zamiri M.J., Derakhshanfar A. Effect of prepubertal exposure to CdCl2 on the liver, hematological, and biochemical parameters in female rats; an experimental study. Biol. Trace. Elem. Res. 2020; 194(2): 472-81. https://doi.org/10.1007/s12011-019-01800-9Mężyńska M., Brzóska M.M. Review of polyphenol-rich products as potential protective and therapeutic factors against cadmium hepatotoxicity. J. Appl. Toxicol. 2019; 39(1): 117-45. https://doi.org/10.1002/jat.3709Mężyńska M., Brzóska M.M. Review of polyphenol-rich products as potential protective and therapeutic factors against cadmium hepatotoxicity. J. Appl. Toxicol. 2019; 39(1): 117-45. https://doi.org/10.1002/jat.3709Rikans L.E., Yamano T. Mechanisms of cadmium-mediated acute hepatotoxicity. J. Biochem. Mol. Toxicol. 2000; 14(2): 110-7. https://doi.org/10.1002/(sici)1099-0461(2000)14:2<110::aid-jbt7>3.0.co;2-jRikans L.E., Yamano T. Mechanisms of cadmium-mediated acute hepatotoxicity. J. Biochem. Mol. Toxicol. 2000; 14(2): 110-7. https://doi.org/10.1002/(sici)1099-0461(2000)14:2<110::aid-jbt7>3.0.co;2-jAndjelkovic M., Buha Djordjevic A., Antonijevic E., Antonijevic B., Stanic M., Kotur-Stevuljevic J., et al. Toxic effect of acute cadmium and lead exposure in rat blood, liver, and kidney. Int. J. Environ. Res. Public Health. 2019; 16(2): 274. https://doi.org/10.3390/ijerph16020274Andjelkovic M., Buha Djordjevic A., Antonijevic E., Antonijevic B., Stanic M., Kotur-Stevuljevic J., et al. Toxic effect of acute cadmium and lead exposure in rat blood, liver, and kidney. Int. J. Environ. Res. Public Health. 2019; 16(2): 274. https://doi.org/10.3390/ijerph16020274El-Refaiy A.I., Eissa F.I. Histopathology and cytotoxicity as biomarkers in treated rats with cadmium and some therapeutic agents. Saudi J. Biol. Sci. 2013; 20(3): 265-80. https://doi.org/10.1016/j.sjbs.2013.02.004El-Refaiy A.I., Eissa F.I. Histopathology and cytotoxicity as biomarkers in treated rats with cadmium and some therapeutic agents. Saudi J. Biol. Sci. 2013; 20(3): 265-80. https://doi.org/10.1016/j.sjbs.2013.02.004Kim B.M., Lee S.Y., Jeong I.H. Influence of squid liver powder on accumulation of cadmium in serum, kidney and liver of mice. Prev. Nutr. Food Sci. 2013; 18(1): 1-10. https://doi.org/10.3746/pnf.2013.18.1.001Kim B.M., Lee S.Y., Jeong I.H. Influence of squid liver powder on accumulation of cadmium in serum, kidney and liver of mice. Prev. Nutr. Food Sci. 2013; 18(1): 1-10. https://doi.org/10.3746/pnf.2013.18.1.001Lu J., Jin T., Nordberg G., Nordberg M. Metallothionein gene expression in peripheral lymphocytes from cadmium-exposed workers. Cell Stress. Chaperones. 2001; 6(2): 97-104. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC434396/Lu J., Jin T., Nordberg G., Nordberg M. Metallothionein gene expression in peripheral lymphocytes from cadmium-exposed workers. Cell Stress. Chaperones. 2001; 6(2): 97-104. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC434396/Boonprasert K., Ruengweerayut R., Aunpad R., Satarug S., Na-Bangchang K. Expression of metallothionein isoforms in peripheral blood leukocytes from Thai population residing in cadmium-contaminated areas. Environ. Toxicol. Pharmacol. 2012; 34(3): 935-40. https://doi.org/10.1016/j.etap.2012.08.002Boonprasert K., Ruengweerayut R., Aunpad R., Satarug S., Na-Bangchang K. Expression of metallothionein isoforms in peripheral blood leukocytes from Thai population residing in cadmium-contaminated areas. Environ. Toxicol. Pharmacol. 2012; 34(3): 935-40. https://doi.org/10.1016/j.etap.2012.08.002Yamada H., Koizumi S. Lymphocyte metallothionein-mRNA as a sensitive biomarker of cadmium exposure. Ind. Health. 2001; 39(1): 29-32. https://doi.org/10.2486/indhealth.39.29Yamada H., Koizumi S. Lymphocyte metallothionein-mRNA as a sensitive biomarker of cadmium exposure. Ind. Health. 2001; 39(1): 29-32. https://doi.org/10.2486/indhealth.39.29Yang C.C., Lin C.I., Lee S.S., Wang C.L., Dai C.Y., Chuang H.Y. The association of blood lead levels and renal effects may be modified by genetic combinations of Metallothionein 1A 2A polymorphisms. Sci. Rep. 2020; 10(1): 9603. https://doi.org/10.1038/s41598-020-66645-yYang C.C., Lin C.I., Lee S.S., Wang C.L., Dai C.Y., Chuang H.Y. The association of blood lead levels and renal effects may be modified by genetic combinations of Metallothionein 1A 2A polymorphisms. Sci. Rep. 2020; 10(1): 9603. https://doi.org/10.1038/s41598-020-66645-yMcNeill R.V., Mason A.S., Hodson M.E., Catto J.W.F., Southgate J. Specificity of the Metallothionein-1 response by cadmium-exposed normal human urothelial cells. Int. J. Mol. Sci. 2019; 20(6): 1344. https://doi.org/10.3390/ijms20061344McNeill R.V., Mason A.S., Hodson M.E., Catto J.W.F., Southgate J. Specificity of the Metallothionein-1 response by cadmium-exposed normal human urothelial cells. Int. J. Mol. Sci. 2019; 20(6): 1344. https://doi.org/10.3390/ijms20061344Costello L.C., Franklin R.B. A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer. Arch. Biochem. Biophys. 2016; 611: 100-12. https://doi.org/10.1016/j.abb.2016.04.014Costello L.C., Franklin R.B. A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer. Arch. Biochem. Biophys. 2016; 611: 100-12. https://doi.org/10.1016/j.abb.2016.04.014Gaither L.A., Eide D.J. The human ZIP1 transporter mediates zinc uptake in human K562 erythroleukemia cells. J. Biol. Chem. 2001; 276(25): 22258-64. https://doi.org/10.1074/jbc.m101772200Gaither L.A., Eide D.J. The human ZIP1 transporter mediates zinc uptake in human K562 erythroleukemia cells. J. Biol. Chem. 2001; 276(25): 22258-64. https://doi.org/10.1074/jbc.m101772200Franklin R.B., Ma J., Zou J., Guan Z., Kukoyi B.I., Feng P., et al. Human ZIP1 is a major zinc uptake transporter for the accumulation of zinc in prostate cells. J. Inorg. Biochem. 2003; 96(2-3): 435-42. https://doi.org/10.1016/s0162-0134(03)00249-6Franklin R.B., Ma J., Zou J., Guan Z., Kukoyi B.I., Feng P., et al. Human ZIP1 is a major zinc uptake transporter for the accumulation of zinc in prostate cells. J. Inorg. Biochem. 2003; 96(2-3): 435-42. https://doi.org/10.1016/s0162-0134(03)00249-6

The authors declare that there are no conflicts of interest present.