University of Michigan - Dearborn1, Department of Natural Sciences, Dearborn, MI 48128 Western Michigan University2, Chemistry, Kalamazoo, MI 49008
Few studies have looked at the effects of carcinogenic metals on ataxia telangiectasia mutated (ATM) protein. ATM is a serine/threonine kinase that is activated in response to DNA damage. This study focused on determining the effects of potassium dichromate on levels of active ATM in human fibroblasts. Previous work in the laboratory (Tesfai et al. Mutation Research, 416:159 - 168) has shown that preincubation of human fibroblasts with 0.3 μM potassium dichromate 46 hours prior to simultaneous incubation with potassium dichromate and benzo[a]pyrene diolepoxide (BPDE) reduced the mutagenic effects of BPDE. We hypothesize that this effect was due to induction of nucleotide excision repair proteins via an ATM-dependent pathway by chromium. Initially, human fibroblasts were exposed to 0.3 μM potassium dichromate for 46 hours. The levels of active ATM were determined by western blotting using an antibody directed towards the phosphorylated (active) form of ATM. The results of three separate experiments showed no significant difference between chromium treated cells and untreated controls. We then began experiments to see if there was a transient activation of the protein at times earlier than 46 hours. Initial results showed that from 30 minutes-46 hours there was no apparent increase of active ATM. We did, however, note a possible increase in ATM activation between 5-15 minutes of exposure to potassium dichromate. These results are preliminary and need further substantiation.
Robert T. Jones was supported by NSF-REU grant No. DBI-0552517. The work was also supported by FRACASF grant No. 08-011 from Western Michigan University.
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