Comparison of hprt variant frequencies and chromosome aberration frequencies in lymphocytes from radiotherapy and chemotherapy patients: a prospective study.
The autoradiographic 6-thioguanine-resistant mutant lymphocyte assay and a chromosome aberration assay were used to determine the time-course of appearance and persistence of elevated frequencies of hprt variants and dicentric chromosomes in patients receiving x-irradiation therapy. Twelve cancer patients, treated with 180-200 cGy/day, 5 days/wk, for 3-7 wk, were studied before treatment, at various weekly intervals during treatment, and after treatment. The hprt mutation assays were done with frozen/thawed lymphocytes isolated from aliquots of the same blood samples used for the chromosome aberration assays. The hprt variant frequencies (Vfs) of only 4 of the 7 patients assayed at 2 wk of treatment were elevated over pre-treatment Vfs, but during the 3rd and 4th weeks of treatment there were significant (P less than 0.01) 5- to 15-fold increases in all Vfs. By 6-32 wk after treatment Vfs had fallen to levels only slightly higher than the mean pre-treatment Vf. The frequencies of cells with dicentric chromosomes were significantly increased (P less than 0.01) after 1 wk of radiotherapy, continued to increase during therapy, and remained elevated after treatment. Five multiple sclerosis patients were also studied before and at 2 and 4 wk intervals after treatment with monthly i.v. doses of 750 mg/m2 of cyclophosphamide (CP). There were no significant elevations in chromosome aberrations at these post-treatment sample times. Previous assays for hprt mutants, done with aloquots of the same blood samples (Ammenheuser et al.: Mutat Res 204:509-520, 1988), had shown 8- to 20-fold increases in Vfs 2 wk after the 1st CP treatment. Our results demonstrate the complementary nature of these two human monitoring assays and emphasize the importance of careful selection of optimal sampling times.
Ammenheuser
M M
MM
Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston 77550.
Au
W W
WW
Whorton
E B
EB
Belli
J A
JA
Ward
J B
JB
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000528:radiation effects; D003520:Cyclophosphamide / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008214:Lymphocytes / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D009152:Mutagenicity Tests; D011878:Radiotherapy / Q000009:adverse effects*; D013997:Time Factors; D014594:Uterine Neoplasms / Q000532:radiotherapy; D014965:X-Rays
D000970:Antineoplastic Agents; D003520:Cyclophosphamide; D007041:Hypoxanthine Phosphoribosyltransferase