Chromosomal sensitivity of lymphocytes from individuals with therapy-related acute nonlymphocytic leukemia.
A small fraction of those individuals exposed to cytotoxic chemotherapy or radiation for the treatment of a primary malignant disease will develop a second malignancy some time later. Although exposure to the cytotoxic agents is believed to be the causative factor, the reason only certain individuals develop the second malignancy is unknown. Some studies have suggested that these individuals might be predisposed to cancer because of an inherent sensitivity to the alkylating agents used in cancer therapy. We have reported that these individuals with therapy-related acute nonlymphocytic leukemia (t-ANLL) have reduced endogenous levels of the repair protein O6-alkylguanine alkyltransferase (AGT). To further investigate the etiology of this disease, alkylation-induced sister-chromatid exchange (SCE) formation in individuals who developed second malignancies, was compared to other patient groups and normal controls. Peripheral blood lymphocytes from patients with (1) t-ANLL, (2) primary forms of acute nonlymphocytic leukemia (ANLL de novo), (3) patients with primary malignancies at risk of developing secondary disease, and (4) unexposed, healthy controls were treated in vitro with N-methyl-N'-nitro-nitrosoguanidine or mitomycin C. Baseline and mutagen-induced frequencies of SCEs were determined. These studies failed to detect any increased sensitivity in those patients who developed second malignancies as compared to controls or patients with de novo forms of the same disease. Also, no correlation between sensitivity to the alkylating agent N-methyl-N'-nitro-nitrosoguanidine and endogenous levels of the AGT repair protein was found. These results suggest that t-ANLL patients are not sensitive to SCE induction by either MNNG or MMC.(ABSTRACT TRUNCATED AT 250 WORDS)
Schwartz
J L
JL
Department of Radiation and Cellular Oncology, University of Chicago, IL 60637.
Karrison
T
T
Le Beau
M M
MM
Larson
R A
RA
Sagher
D
D
Strauss
B
B
Rowley
J D
JD
Weichselbaum
R R
RR
D000970:Antineoplastic Agents / Q000009:adverse effects*; D004261:DNA Replication / Q000187:drug effects; D006689:Hodgkin Disease / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000139:chemically induced* / Q000201:enzymology; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D008297:Male; D008769:Methylnitronitrosoguanidine; D008780:Methyltransferases / Q000097:blood; D016685:Mitomycin; D008937:Mitomycins; D019853:O(6)-Methylguanine-DNA Methyltransferase; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D000970:Antineoplastic Agents; D008937:Mitomycins; D008769:Methylnitronitrosoguanidine; D016685:Mitomycin; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase