Hprt mutations and karyotype abnormalities in T-cell clones from healthy subjects and melphalan-treated ovarian carcinoma patients.
In vivo mutations at the locus for hypoxanthine phosphoribosyl transferase (hprt) were studied in 6-thioguanine (TG)-resistant T-lymphocyte clones from healthy male and female subjects and ovarian carcinoma patients treated with melphalan. Southern blot analysis of 108 clones showed alterations in 14% (4/29) of the clones from healthy males, 4.3% (2/47) of the clones from healthy females and 3.1% (1/32) of the clones from melphalan-treated patients. 2 of the 7 abnormal clones had a total deletion of the hprt gene; the others had partial deletions. Karyotype analysis of 82 clones revealed 1 clonal abnormality in 29 mutant clones from healthy males (3.6%). Loss or structural aberration of 1 X-chromosome occurred in 6% of the clones from healthy females. The frequency of karyotypic abnormalities (excluding those affecting one of the X-chromosomes) was significantly higher in clones from patients (37%) as compared to healthy females (5.9%). No aberration was found to affect the hprt locus at Xq27 in any of the 82 clones studied.
Department of Clinical Genetics, Karolinska Hospital, Stockholm, Sweden.
S M
SM
He
K
K
Holmberg
B
B
Lambert
N
N
Einhorn
D015139:Blotting, Southern; D002277:Carcinoma / Q000188:drug therapy; D002869:Chromosome Aberrations / Q000473:pathology*; D025063:Chromosome Disorders; D002999:Clone Cells; D005260:Female; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007621:Karyotyping; D008558:Melphalan / Q000009:adverse effects; D009154:Mutation; D010051:Ovarian Neoplasms / Q000188:drug therapy; D013601:T-Lymphocytes / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure
D007041:Hypoxanthine Phosphoribosyltransferase; D008558:Melphalan