Mechanisms of toxicity 1

Example of uptake transporter

SLC22, organic cations and anions

Want poor absorption=less toxicity

Cascade

The target determines the response by initiating signalling and cellular stress, if stress reaches a threshold cells must decide to repair or die

Common poison targets?

Transmembrane receptors, cytotoxic proteins, nucleic acids DNA and RNA

Mechanisms of stress induction

Can either cause it directly, most produce reactive species through redox cycling. Eventually homeostatic systems can’t restore balance

Cellular dysfunction- injury- death

What plays a deciding role in cell death

Mitochondria

Two classes of cellular dysfunction

• Cell signalling : Gene expression, electrical excitability

• Cell maintenance : Internal, external

Three categories of disrepair

• Molecular: protein, lipid, DNA

• Cellular

• Tissue: Apoptosis, proliferation

4 steps to toxicity

1. Delivery

2. Interaction with target

3. Cellular dysfunction

4. Dysrepair