TY - JOUR
T1 - Baseline and phosphoramide mustard-induced sister-chromatid exchanges in pharmacists handling anti-cancer drugs
AU - McDiarmid, Melissa A.
AU - Kolodner, Ken
AU - Humphrey, Frances
AU - Putman, Donald
AU - Jacobson-Kram, David
PY - 1992/6/1
Y1 - 1992/6/1
N2 - 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 <0.0001 for low-dose PM challenge (0.1 mg/ml PM) and r = 0.67 (p <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 <0.0001) for low-dose PM and r = 0.59 (p <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.
AB - 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 <0.0001 for low-dose PM challenge (0.1 mg/ml PM) and r = 0.67 (p <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 <0.0001) for low-dose PM and r = 0.59 (p <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.
KW - Baseline SCE
KW - Cyclophosphamide
KW - Pharmacists handling anti-cancer drugs
KW - Phosphoramide mustard-induced SCE
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U2 - 10.1016/0165-1218(92)90067-A
DO - 10.1016/0165-1218(92)90067-A
M3 - Article
C2 - 1377335
AN - SCOPUS:0026734303
SN - 0165-1218
VL - 279
SP - 199
EP - 204
JO - Mutation Research/Genetic Toxicology
JF - Mutation Research/Genetic Toxicology
IS - 3
ER -