Chromosomal effects of non-alkylating drug exposure in oncology personnel.
Therapy-related leukemia has been a recognized sequela of cancer treatment for decades with "signature" abnormalities of chromosomes 5, 7, and 11 observed in treated patients. Risk to oncology personnel handling anti-cancer agents has also been documented by non-specific measures of genotoxicity in blood and urine. Using chromosomal markers applied in clinical practice, we previously demonstrated in oncology workers, a dose-related increase in abnormalities of chromosomes 5 and 7, known to be targets of alkylating agent exposure. In the analysis presented here, we extended that work to also assess damage resulting from non-alkylating drug exposure. Peripheral blood lymphocytes from oncology personnel (N = 63) and non-exposed controls (N = 46) was collected and examined using the fluorescent in situ hybridization technique with probes for targets on chromosomes 5, 7, and 11. Participants recorded drug handling events over a 6 week period. Important co-variates were considered. Examining chromosomal outcomes as a function of drug handling frequency, we employed Poisson Regression to obtain incident rate ratios (IRRs) for selected drug handling frequencies. We found a dose-related increase in the IRR for aberrations in all three chromosomes 5, 7, and 11, reaching statistical significance for chromosome 5, as a function of non-alkylating drug handling. This suggests that the targeting of chromosome 5 is not limited to alkylating agent exposure, as some recent evidence in treated patients has also shown. Thus, the pattern of insult observed in treated patients appears to extend to oncology personnel exposed in the workplace.
University of Maryland School of Medicine, Baltimore, Maryland.
Melissa A
MA
McDiarmid
Bonnie
B
Rogers
Marc S
MS
Oliver
D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000097:blood; D016022:Case-Control Studies; D002869:Chromosome Aberrations / Q000139:chemically induced*; D002880:Chromosomes, Human, Pair 11 / Q000187:drug effects* / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000187:drug effects* / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000187:drug effects* / Q000235:genetics; D005260:Female; D006282:Health Personnel; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D008495:Medical Oncology; D016273:Occupational Exposure / Q000009:adverse effects* / Q000032:analysis
D000970:Antineoplastic Agents
anti-cancer drugs; chromosome; oncology worker