Exam 2 Flashcards
3 natural absorption routes
oral, respiratory, dermal
experimental exposure routes
IM, IP, IV, subcutaneous
the initial metabolism that a substance undergoes in the liver and gut wall after absorption from the GI tract, before the substance enters the systemic circulation
first pass metabolism
first pass route of ingestion steps
- small intestine absorption
- hepatic portal vein
- liver
- hepatic vein to heart
steps of hepatobiliary circulation
- liver to bile
- bile secreted in small intestine
- enterocyte absorption
- return to liver via portal vein
the process by which a toxic substance enters the body and is taken up by the tissues, organs, and fluids
absorption
the process by which absorbed toxicants travel to other tissues with varying levels of efficiency (depends on the chemistry of the substance)
distribution
the process by which an absorbed substance is chemically altered to aid in the overall excretion of it from the body
metabolism
the passive process by which a substance is removed from the body (via filtration, secretion, and reabsorption)
excretion
the process by which a substance undergoes the irreversible removal of a toxicant via metabolism and excretion
elimination
this is a process of metabolism that alters a substance through oxidation, reduction, or hydrolysis to aid in its removal
Phase 1 toxicant metabolism
this is a process of metabolism that often involves the conjugation of a substance with small molecules (like sulfate, glutathione, or AAs) to further aid in their elimination
Phase 2 toxicant metabolism
one of the most important Phase 1 metabolism enzymes; responsible for the production of many bioactivated toxicants
Cytochrome p450
4 derivatives of cyt450
cyp2e1, cyp3a, cyp2c, cyp1a2
This condition can be caused by exposure to toxicants and involves a significant reduction in the level of GSH in the body
glutathione depletion
this describes certain substances that often increase the rate at which another substance can be bioactivated; often resulting in the overactivation of certain phase 1 enzymes
cyt p450 inducers
programmed cell death; regulated, timely, and minimally damaging to surrounding tissues
apoptosis
cell death; usually induced by stressors, unregulated, damaging and inflammatory to surrounding tissues
necrosis
cellular changes of apoptosis
- shrinkage
- loss of cell membrane
- loss of nuclear membrane
- DNA fragmentation
apoptosis requirements
- ability to make protein
- energy production
a normal gene that can potentially become a gene that contributes to the development of cancer; normally regulate cell growth and division
proto-oncogene
a gene that contributes to the development of cancer
oncogene
a subcellular fraction of a homogenized tissue that contains cytosolic and microsomal enzymes, including cytochrome P450 enzymes; used in the Ames test
S9 fraction
the process by which heritable changes in gene expression occur without a change in the underlying DNA sequence; can be caused by exposure to toxicants or stress
epigenetic promotion
Potential carcinogens that bind to the regulatory domain of PKC, causing a conformational change that allows the enzyme to become active
Phorbol esters
any substance, organism, physical agent, or deficiency that can cause abnormal development/death in an embryo or fetus
teratogen
