cell line for cytotoxicity assay

[Dispen]

In my experiment, I use a HepG2 cell line for a cytotoxicity assay with Alamar Blue dye, to test toxicities of different metal ions on the liver cells. HepG2 is a liver carcinoma cell line from a Homo Sapiens (human) origin. I know that usually liver cell is used for cytotoxicity assay, however, I wonder what will happen if I use brain cell line instead? And what if I use rat cells instead of human cells? I noticed a study comparing a mouse neuroblastoma line (neuro-2a) to primary neurons found that neuro-2a cells were much less sensitive to neurotoxins, possibly due to a lack of important membrane receptors and ion channels. It means that some neuronal cell lines produce undesirable unrepresentative results. Also, neuronal cells are usually used for investigation of neurotoxicity but not toxicity to human via normal routes of toxic substance intake and degradation, i.e. detoxification in liver. Nonetheless, does it mean the results produced by neuronal cell line will be very different compared with by HepG2? 

If I use rats instead of human liver cell line, I think the results will be similar but the dose used to produce the same response level may be lower because rats are much smaller in size than human? Am I right?

[CharonY]

Unfortunately it is often difficult to predict how different cell lines react to certain chemicals. There are certain cell lines which are considered more hardy, and often e.g. primary cell lines are more sensitive than many carcinomas. HepG2 is often used as it is a bit less resilient (and probably less full of viruses) compared to e.g. HeLa, but there are folks who prefer to use primary cell lines, as the results are probably closer in vivo conditions. But there is no simply way to extrapolate those values (to my knowledge) and most data is obtained empirically.

In other words, HepG2 data can not be easily translated to other cell lines. Using whole animals things are getting more complicated. Remember, the dose you use directly at the cell is independent on the animal (as we work on the cellular level). However, during in vivo experiments you will need to account for the interaction of the chemical with the body (ADME- absorption, distributon, metabolism, excretion). I.e. if you apply the chemical to a rat, depending on how you apply it (e.g. orally, intravenously), the bioavailability of the chemical and how it is metabolized will determine how much will actually end up in the liver to do damage. Moreover, metabolization can inactive it (e.g. making it more hydrophilic and eliminate from the body quicker than the original compound) or conversely make it more toxic. There is a reason why in many cases we still rely on animal data, rather than solely on cell lines to assess human toxicity.

[Dispen]

On 11/17/2019 at 3:35 PM, CharonY said:

Unfortunately it is often difficult to predict how different cell lines react to certain chemicals. There are certain cell lines which are considered more hardy, and often e.g. primary cell lines are more sensitive than many carcinomas. HepG2 is often used as it is a bit less resilient (and probably less full of viruses) compared to e.g. HeLa, but there are folks who prefer to use primary cell lines, as the results are probably closer in vivo conditions. But there is no simply way to extrapolate those values (to my knowledge) and most data is obtained empirically.

In other words, HepG2 data can not be easily translated to other cell lines. Using whole animals things are getting more complicated. Remember, the dose you use directly at the cell is independent on the animal (as we work on the cellular level). However, during in vivo experiments you will need to account for the interaction of the chemical with the body (ADME- absorption, distributon, metabolism, excretion). I.e. if you apply the chemical to a rat, depending on how you apply it (e.g. orally, intravenously), the bioavailability of the chemical and how it is metabolized will determine how much will actually end up in the liver to do damage. Moreover, metabolization can inactive it (e.g. making it more hydrophilic and eliminate from the body quicker than the original compound) or conversely make it more toxic. There is a reason why in many cases we still rely on animal data, rather than solely on cell lines to assess human toxicity.

Thanks a lot !