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Carcinogenic Metals

Carcinogenic Metals. International Agency for Research on Cancer (IARC) classification. Group 1: Confirmed human carcinogens As, Be, Cd, Cr(VI), Ni Group 2B: Possibly carcinogenic to humans Co. A model summarizing the major mechanisms involved in Cd carcinogenesis.

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Carcinogenic Metals

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  1. Carcinogenic Metals International Agency for Research on Cancer (IARC) classification Group 1: Confirmed human carcinogens As, Be, Cd, Cr(VI), Ni Group 2B: Possibly carcinogenic to humans Co

  2. A model summarizing the major mechanisms involved in Cd carcinogenesis

  3. Categories of Genes Induced by Cd • Immediate early response genes (IEGs) • Stress response genes • Transcription factors • Translation factors • Miscellaneous genes

  4. Some of the genes induced by cadmium Translational Genes Transcription Factors MTF1 USF NFκB Nrf2 Translation initiation factor 3 Translation elongation factor 1δ

  5. FAS-initiated apoptotic cascade

  6. Proposed pathways for ROS in Cd toxicology and carcinogenesis following acute and chronic exposures

  7. Structure of residues 19 – 44 of β-Catenin phosphorylated on Ser 33 and 37 Oncogenic mutations in codon 33: TCT → TAT Ser → Tyr TCT → TTT Ser → Phe

  8. Role of β-catenin in Wnt signaling pathway Proteasome: protein complex that degrades tagged proteins The α-cadherin/β-Catenin complex connects to the actin via α-Catenin and some actin-binding proteins, forming a rigid cytoskeleton. When cells are exposed to Wnt signal, cell surface receptors are activated and block β-Catenin phosphorylation and its subsequent ubiquitination. β-Catenin is thus diverted from the proteasome, and it accumulates and enters the nucleus, where it finds a partner of the TCF/LEF family. Together, they activate new gene expression programs.

  9. Chromium uptake, intracellular chemistry and damage

  10. Chromium-DNA Adducts

  11. Pathways leading to observation of single-strand DNA breaks (SSB) and double-strand DNA breaks (DSB)

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