Re: Why does the drug, Chloroquihne induce large vacuoles within cells?

I am sorry it took me a few days to get back to you about this. Without seeing the paper you are looking at, it's difficult for me to specifically respond with a clear answer but I can give you some possibilities. One thing you can consider is the vehicle for the drug. Many drugs are dissolved in compounds like ethanol or dimethyl sulfoxide (DMSO), both of which should not be added to cells at a concentration of 1% of the total solution volume. Consult your paper and see what they resuspended their chloroquine in, I checked the catalog information for chloroquine from Sigma (see below) and Chloroquine is water-soluble, so I was doubtful that the researchers would have used anything else--you always use water if you can get away with it because it makes the cells happier. If they did use something else, consider what they used and at what concentration--organic solvents used at a concentration over 1% of the solution volume will make strange things happen. Another thing to consider is the concentration at which the Chloroquine was used. Do you know what the typical working concentration is? The product page for Chloroquine at the Sigma website has some references at the bottom of the page you could use to check. Keep in mind that adding high concentrations of a drug will cause the cells to have unphysiological responses in some cases, and these vacuoles may be just such an example. If you look at the product information sheet for Chloroquine, you'll see that it can do a few interesting things--intercalate DNA, and disrupt antigen-antibody complexes, and it's working concentration for this application is 200 mg/ml, so if it's used above that, it could have had an unusual effect on the cells. The overarching theme here is that you should always consider, when a drug or compound is applied to cells, what the in vivo relevance of that application will be, and if it's a compound that's normally found in the cell, how close to physiological conditions are the experimental conditions? Obviously, you want them to be as close as possible. What kind of cells were used, and how were they grown? Were there any other aspects of their growth conditions that could have made them unhappy? I think the better explanation is that a high concentration of Chloroquine was used and the cells responded in an unusual way, but without the paper I can't tell, so I hope these ideas will help you keep it moving. If you want to email in the reference for your paper I can take a look at it and get back to you with more specific ideas. Sigma Search for chloroquine in the search bar at upper right corner, and you can look at the product information if you choose the Chloroquine diphosphate salt link and look at the Product Information Sheet under related information on the right side of the product page.