Determinations of baseline and
mutagen-induced sister-chromatid exchanges (SCE) have been used as indicators of previous
mutagen exposure in several human populations.
Mutagen-induced SCE is based on the premise that a genetic outcome may depend not only on a present exposure, but also on a cell's "memory" of previous exposure. The genotoxicity of some anti-
cancer drugs including
cyclophosphamide (CP) has been studied by determining baseline and
mutagen-induced SCE in peripheral blood lymphocytes in treated
cancer patients. This study examined the in vivo genotoxic effects of occupational exposure to anti-
cancer drug handling by relating baseline and
phosphoramide mustard (PM) -induced SCE levels with duration of anti-
cancer drug handling as a surrogate for anti-
cancer drug exposure dose. The mean baseline SCE for the population was 5.19 +/- 0.17 and was not correlated with duration of
drug handling. However, a strong correlation was demonstrated between inducible SCE values and life-time duration of
drug handling with r = 0.63 (p less than 0.0001 for low-dose PM challenge (0.1 mg/ml PM) and r = 0.67 (p less than 0.0001) for high-dose PM challenge (0.25 mg/ml PM). A similar relationship was seen for PM-induced SCE and duration of anti-
cancer drug handling for the workers' present job with correlations obtained being r = 0.63 (p less than 0.0001) for low-dose PM and r = 0.59 (p less than 0.0001) for high dose PM. The short-lived nature of the baseline SCE lesion is discussed as a limitation in population surveillance studies, as it reflects primarily recent
mutagen exposure and persists only for days to weeks after exposure. The induced SCE measure is postulated to provide an integrating
dosimeter of remote previous exposure, improving upon the current limitation of the baseline SCE measure and allowing the "unmasking" of previous exposure in a provocative framework.