MODIFICATION OF THE SENSITIVITY AND REPAIR OF POTENTIALLY LETHAL DAMAGE BY DIETHYLDITHIOCARBAMATE DURING AND FOLLOWING EXPOSURE OF PLATEAU-PHASE CULTURES OF MAMMALIAN-CELLS TO RADIATION AND CIS-DIAMMINEDICHLOROPLATINUM(II)

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (8) , 3074-3078
Abstract
Diethyldithiocarbamate (DDC), a chelating agent known to reduce levels of superoxide dismutase and glutathione peroxidase, appears to protect irradiated monolayers of mammalian cells [Chinese hamster ovarian fibroblast HA-1 cells] when present for 1 h before and during irradiation. To examine a possible cause of this modification, the repair of potentially lethal X-ray damage was examined with and without the presence of DDC in the medium overlying the cells postirradiation. Although little repair was seen in full medium alone, when DDC was added to the full medium, the amount of repair was comparable to that seen under optimum repair conditions, i.e., in Hanks'' balanced salt solution. The t1/2 [half-time] of the repair process in Hanks'' balanced salt solution or in full medium with DDC added was comparable and of the order of 1-1.5 h. The cis-platinum sensitivity of the monolayers is significantly modified by the addition of DDC; the nature of the modification is dependent upon the time at which the DDC is added to the cells following initiation of cis-platinum exposure. To investigate a possible reason for this protection by DDC, the repair of potentially lethal cis-platinum damage was examined in the cell monolayers. Minimal repair was noted in the presence of Hanks'' balanced salt solution or full medium; when DDC was added to the full medium, the repair was tripled and the t1/2 of the repair process was .apprx. 2 h. The ability of DDC to protect cells from exposure to both X-rays and cis-platinum, together with its augmentation of repair of potentially lethal damage following exposure to each, has broad clinical application and is being actively explored in tumor-bearing mice.