DNA damage and differential cytotoxicity produced in human cells by 2-chloroethyl (methylsulfonyl)methanesulfonate (NSC 338947), a new DNA-chloroethylating agent.
2-Chloroethyl (methylsulfonyl)methanesulfonate (CIEtSoSo) is of interest as a possible new chloroethylating agent because its simpler chemistry suggests that it will not generate the hydroxyethyl products which are produced by chloroethylnitrosoureas (CIEtNUs). The effects of CIEtSoSo on DNA were studied in IMR-90 and VA-13 human embryo cells by means of DNA alkaline elution analysis. IMR-90 are normal cells, whereas VA-13 cells are SV40 transformed and are deficient in DNA-guanine O6-alkyltransferase activity. The effects of CIEtSoSo were essentially the same as those of CIEtNUs in the following respects: DNA interstrand cross-links were produced in VA-13 cells but not in IMR-90 cells; the interstrand cross-links in VA-13 cells were formed after a delay of 6 to 12 h and appeared to undergo repair; DNA-protein cross-links were formed promptly in both cell types and appeared to be repaired; DNA strand breaks and alkali-labile lesions were produced and repaired, and differences were observed between the two cell types; and VA-13 cells were more sensitive than IMR-90 cells (dose modification factor, 5). The differential cytotoxicity against VA-13 cells was similar to that produced by noncarbamoylating CIEtNUs, and significantly larger than that produced by carbamoylating CIEtNUs. The results suggest that CIEtSoSo acts by chloroethylating guanine O6 positions in DNA.
Gibson
N W
NW
Erickson
L C
LC
Kohn
K W
KW
D000478:Alkylation; D000970:Antineoplastic Agents / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008698:Mesylates / Q000633:toxicity*
D000970:Antineoplastic Agents; D008698:Mesylates; C041189:clomesone; D004247:DNA