Chinese hamster V79 cells and their
arsenite-resistant variants were found to have an
arsenite- and
antimonite-inducible tolerance mechanism which protects against the subsequent cytotoxic effects of
arsenate,
arsenate and
antimonite. Inducible tolerance requires de novo
mRNA and
protein synthesis, and is independent of the heat shock response. In contrast, we report that the
arsenite hypersensitive variant line As/S27D lacks the inducible tolerance response. Numerous attempts were made to detect an inducible tolerance response to
arsenite in a variety of human cells. An assay based on
Neutral red uptake was used in order to study inducible tolerance in cells with poor clonability. Neither normal diploid cells nor human
tumor cells of different origins were found to elicit an inducible tolerance response to
arsenite. This finding may help to explain why rodents do not develop
tumors after exposure to
arsenite, while humans do. In addition, all human cell lines tested were much more sensitive to
arsenite compared to Chinese hamster cells. Human keratinocytes were especially sensitive. In general, human cells resemble
arsenic hypersensitive Chinese hamster As/R27D cells, which have lost a protective mechanism found in wild-type Chinese hamster cells.