Gene-specific DNA interstrand cross-links produced by nitrogen mustard in the human tumor cell line Colo320HSR.
Genomic and gene-specific DNA interstrand cross-links produced by nitrogen mustard (HN2) were measured in the human tumor cell line Colo320HSR. Following exposures that produced greater than or equal to 1 log cell kill, it was found that HN2-induced DNA interstrand cross-links were produced and processed in a heterogeneous fashion within the genome. Cross-links were detected in the amplified, overexpressed c-myc oncogene, whereas in the weakly expressed N-ras gene and the nontranscribed, high copy number alpha-satellite sequence (of chromosome 20), cross-links were not detected. The cross-links in the c-myc oncogene disappeared more rapidly than total genomic cross-links. These results suggest that HN2-induced DNA interstrand cross-links are produced and processed in the genome in a nonrandom fashion.
Futscher
B W
BW
Department of Pharmacology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153.
Pieper
R O
RO
Dalton
W S
WS
Erickson
L C
LC
D015139:Blotting, Southern; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D004249:DNA Damage; D015342:DNA Probes; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects*; D011905:Genes, ras / Q000187:drug effects*; D006801:Humans; D008466:Mechlorethamine / Q000494:pharmacology*; D009691:Nucleic Acid Denaturation; D014407:Tumor Cells, Cultured / Q000187:drug effects
D015342:DNA Probes; D004273:DNA, Neoplasm; D008466:Mechlorethamine