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Carcinogenic Metals International Agency for Research on Cancer (IARC) classification Group 1: Confirmed human carcinogens As, Be, Cd, Cr(VI), Ni Group.

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Presentation on theme: "Carcinogenic Metals International Agency for Research on Cancer (IARC) classification Group 1: Confirmed human carcinogens As, Be, Cd, Cr(VI), Ni Group."— Presentation transcript:

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 Translation initiation factor 3 Translation elongation factor 1δ Transcription Factors MTF1 USF NFκB Nrf2

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)

12


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