Baseline and mutagen-induced sister chromatid exchanges in lymphocytes of pharmacists handling anticancer drugs

Biomonitoring of pharmacists for exposure to alkylating anticancer drugs including cyclophosphamide (CP) was performed by determining baseline and phosphoramide mustard (PM)-induced sister chromatid exchanges (SCEs). Determinations of baseline SCEs have been used as indicators of mutagen exposure in a number of occupational studies of exposed workers. The relatively short-lived nature of the DNA lesion (days to weeks) has limited the usefulness of the SCE marker in cross-sectional or periodic surveillance studies of workers because a lesion may have been repaired prior to the sampling period. Recent reports indicate that exposure to mutagens may induce genetic instability that renders cells more susceptible to experimental mutagen challenges. Such a method was employed in the present study to assess risks to pharmacists associated with handling antineoplastic drugs. The present study was designed to further characterize our observation of a strong correlation between duration of pharmacist drug handling (exposure measure) and susceptibility of their lymphocytes to PM -induced SCE. In the present study the mean baseline SCE for the pharmacist population was 6.51 ± 0.53 and was not correlated with duration of drug handling, presumably due to current safe handling procedures. The PM - induced SCE values at high-dose PM (0.25 μg/ml PM), however, did show a significant correlation to duration of drug handling with r = 0.37 (p = 0.045) This correlation was not seen with the low-dose PM challenge (0.1 μg/ml PM) or when the SCE-inducing agents were varied using ethyl methanesulfonate (EMS) or mitomycin C (MMC). Results suggest that exposure to antineoplastic drugs produces a type of genetic instability that renders cells more sensitive to certain mutagenic challenges at high doses. These methods provide additional tools for biomonitoring of mutagen-exposed populations.