Nickel Flashcards
what is a very toxic form of nickel that is poisonous
Ni + CO = nickel carbonyl Ni(CO)4
how is Ni(CO)4 taken into the body
via inhalation
where does Nickel compounds accumulate
within connective tissue of the lungs
what is the clearance rate of Nickel compounds + why
slow bc they accumulate within connective tissue of the lungs
how long can Nickel compound intoxication occur + initial symptoms
hours or days after exposure, initially mild symptoms (headache, dizziness, nausea)
what causes primary Nickel compound toxicity
glutathione depletion and binding to sulfhydryl groups
where is primary injury from Nickel compounds
alveoli
when does maximum damage occur to alveoli with Nickel compound exposure
4-6 days after exposure
what can happen with heavy Nickel compound exposure
progress to pneumonia, respiratory failure, cerebral edema and death
where are Nickel compounds carcinogenic
in the respiratory system - nasal (large particles) and lungs (small particles)
what happens when Nickel compounds get to the target cells
they are phagocytized then stored in acidic vacuoles (lysosomes) which release the nickel
what happens when Nickel is released in the target cells
high intracellular concentration in cytoplasm (insoluble) and nucleus (soluble)
where in the cell does insoluble Ni go
in the cytoplasm
where in the cell does soluble Ni go
in the nucleus
what does clastogenic mean
they disrupt and break chromosomes
what happens with phagocytosed Ni particles with high concentration to the nucleus
they are clastogenic rather than mutagenic
are phagocytosed Ni particles with high concentration to the nucleus clastogenic or mutagenic
clastogenic
what does crystalline nickel sulfide compounds do (what kind of damage)
specific chromosomal damage esp in long arm of X chromosome (decondensation, frequent deletions, etc)
what is the mechanism for clastogenic damage by Ni
unclear but maybe because Ni can affect Ca++ entry into cells & intracellular Ca++ levels
what do calcium chelators do to nickel
inhibit nickel induced clastogenesis
what kind of genes have changed expression with Ni present + increase or decrease
increase HIF-1 and Ect2
what is HIF-1 (acronym and role)
Hypoxia inducible factor - increased angiogenesis and glucose transport, shifts organism from aerobic to anaerobic metabolism
what is Ect2 (role)
controls DNA synthesis - microtubule disassembly resulting in morphological changes
what can Ni do to genes
alter methylation
what kind of genes are effected when Ni methylates genes
tumor suppressors
how does Ni alter tumor suppressors (2) + net effect
replacing the ferrous iron in the catalytic centers of histone demethylase and DNA repair enzymes - silenced genes
how does Ni effect DNA binding proteins + net effect
Ni replaces Zn in zinc fingers to alter the conformation of the protein - effects activation & inactivation of genes
what do Zn fingers do
allow DNA binding proteins to interact with DNA strand grooves
