Primary cells vs. cell line: which is more resistant?

[hanhan2008]

Which is generally more resistant to toxicants?
1. Stem cells vs. differentiated cells.
2. Primary cells vs. cell line
3. Immortalized cell line vs. non-immortalized cell line.
It'll be great if somebody could give some links to some research papers on these topics.
Thanks!

[biohazard]

1. I would guess some differentiated cells are more resistant than their stem cells. E.g. cells that do not really divide any more (muscle cells, neurons etc.) are very resistant to toxins that affect cell cycle, and for the same reason they are also able to tolerate much higher radiation doses (which is not a toxin as such, though)

2. I think this depends on the cells we're talking about; not sure though what the actual answer is.

3. Immortalized vs. mortalized - again, this probably depends strongly on the toxin and cells in question, again immortalized cells often divide quickly, and could be prone to cell cycle -targeting toxins, but they often mutate quite fastly and could maybe generate different resistances easier.

[MrMistery]

i don't think there is an answer to 2 or 3. At least for 2: if you are working with a line you will probably be able to make better predictions than with primary cells, but that doesn't mean it will react better.

[hanhan2008]

Thanks a lot, guys! One frequent criticism from in vivo people on cell culture studies using lung epithelial cell lines is the comparability or generability of in vitro results to in vivo situation since in many cases, it takes unrealistically high doses to cause a measurable effect in cultured cells (in vivo doses are much much smaller since the lung has a huge surface area). If an in vivo relevant dose is used in vitro, one may not really get the same effect. While this argument has a point, I want to argue for the relevance of in vitro studies: lung epithelial cell lines are probably more resistant than primary cells or their counterparts in vivo. Therefore, an in vitro effect in cultured cells only seen at high doses of a certain chemical does not necessarily mean that the chemical is safe to animals or humans at relevantly lower doses. In this case, in vitro study is still a valuable tool because it points out the right directions to go for animal studies, though virtually any results from in vitro studies need to be confirmed by animal studies.

[MrMistery]

in vitro studies are very useful to study mechanisms of action - for example the lab i work at studies how certain chemicals influences parameters like oxidative stress, the levels of certain enzymes etc - to find out what exactly is going on. Doses are generally the least of problems.