@phdthesis{97ef4f0a-9030-4e23-99df-2943d799878c,
  abstract     = {{Hexavalent chromium (Cr(VI)) is classified as a Group 1 human carcinogen and increases the risk of lung cancer because it can generate reactive oxygen species, induce DNA damage, and trigger epigenetic alterations Occupational Cr(VI) exposure can occur during different work processes, but when this PhD study was initiated, the exposure level to Cr(VI) at Swedish workplaces and its health risk were unknown. Within the SafeChrom project, 113 Cr(VI) exposed workers and 72 controls were recruited. Inhalable Cr(VI) was measured by personal air sampling. Cr was measured in urine (U-Cr) and red blood cells (RBC-Cr). Effect biomarkers were measured, including 8-hydroxy-2’-deoxyguanosine (8-OHdG) in urine, relative mitochondrial DNA copy number (mtDNA-cn), relative telomere length (TL), micronuclei in peripheral blood reticulocytes (MNRET), DNA methylation level of four candidate genes, expression levels of three lncRNAs and four miRNAs. After excluding females and current smokers, miRNA sequencing, differentially expressed miRNAs (DEMs) identification, and bioinformatics analysis were conducted. Finally, the expression levels of potential target genes of the DEMs were validated. We found that workers were exposed to low-to-moderate levels of Cr(VI) with a median inhalable Cr(VI) concentration of 0.13 μg/m³. Eight exposed workers (7%) exceeded the Swedish occupational exposure limit of 5 μg/m3. Median U-Cr (0.60 µg/L) and RBC-Cr (0.73 µg/L) were significantly higher in the exposed workers compared with the controls (0.10 and 0.53 µg/L, respectively). Inhalable Cr(VI) correlated with urinary Cr (Spearman’s rank correlation coefficient (rS)=0.64) and RBC-Cr (rS=0.53). Exposed workers had higher levels of 8-OHdG, longer TL, and MGMT promoter methylation, and lower levels of mtDNA-cn and MNRET, compared to controls. TL was positively correlated with U-Cr, while 8-OHdG and MGMT were positively associated with RBC-Cr. Expression levels of lncRNAs MALAT1 and NORAD, and all four miRNAs, were significantly lower in exposed workers compared with controls, and significantly negatively correlated with RBC-Cr concentrations. H19 was significantly correlated with miR-142-3p (rS=-0.33) and miR-15b-5p (rS=-0.30), and NORAD was significantly positively correlated with all four miRNAs (rS=0.17 to 0.46). In the exposed workers, 21 up-regulated and 38 down-regulated DEMs were identified. Target genes of DEMs were significantly enriched in three KEGG terms: miRNAs in cancer, small cell lung cancer and non-small cell lung cancer. The expression of target genes CCNE2, CDK4 and E2F1 was significantly higher in the exposed workers compared with controls. Overall, this thesis reveals that while most workers in Sweden were exposed to low-to-moderate levels of Cr(VI), certain individuals were subjected to high levels of this non-threshold carcinogen. Cr(VI) exposure was associated with notable molecular changes, including oxidative stress, genomic instability, and epigenetic alteration, which stresses that exposure to Cr(VI) should be minimised as much as possible. Multiple mechanisms may interact to drive the toxicity and carcinogenesis associated with Cr(VI) exposure.}},
  author       = {{Jiang, Zheshun}},
  isbn         = {{978-91-8021-822-1}},
  issn         = {{1652-8220}},
  keywords     = {{Hexavalent chromium; Occupational Exposure; Biomonitoring; Toxicity; Effect biomarkers}},
  language     = {{eng}},
  number       = {{2026:24}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Occupational Exposure to Hexavalent Chromium in Sweden and its Toxicity - Evidence from the SafeChrom project}},
  url          = {{https://lup.lub.lu.se/search/files/242446380/Zheshun_Jiang_-_WEBB.pdf}},
  year         = {{2026}},
}