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

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

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

FAS-initiated apoptotic cascade

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

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

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.

Chromium uptake, intracellular chemistry and damage

Chromium-DNA Adducts

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