Comparative carboxylesterase activities in infant and adult liver and their in vitro sensitivity to chlorpyrifos oxon.
Maturational expression of carboxylesterase activity in laboratory animals has been correlated with age-related differences in sensitivity to many organophosphorus insecticides including chlorpyrifos. Little information is available, however, on the maturational expression of liver carboxylesterases in humans. Human liver carboxylesterase activity was compared in tissues from infants (2-24 months) and adults (20-36 years). There was no significant difference between mean infant and adult carboxylesterase activities. The carboxylesterase activity rank order was: 2 months<3 months<20 years<24 months<4 months<36 years<21 years<8 months<34 years<35 years. Proteins (3 microg) were separated and blotted using antibodies against rat hydrolase S (HS), human carboxylesterase (HCE) types 1 and 2, and CYP3A4. Again, there were no significant differences in staining density between infant and adult tissues with any isozyme. Aliquots of each sample were pre-incubated (30 min, 37 degrees C) with chlorpyrifos oxon to evaluate in vitro sensitivity. Based on 95% confidence intervals, no significant differences in IC50 values were obtained in 3-month to 36-year samples (range: 1.42-2.12 nM), while the IC50 was significantly lower in the 2-month sample (0.45 nM). Carboxylesterase activity across samples was correlated with cytochrome b5 content and HS immunosignal but not with other microsomal activities (total cyt P450 content, testosterone hydroxylation, coumarin hydroxylation, and EROD). The results suggest that, in contrast to rodents, human liver carboxylesterase expression changes relatively little during postnatal maturation.
Pope
Carey N
CN
Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA. pcarey@okstate.edu
Karanth
Subramanya
S
Liu
Jing
J
Yan
Bingfang
B
D000328:Adult; D000375:Aging / Q000502:physiology; D043182:Carboxylesterase / Q000378:metabolism*; D004390:Chlorpyrifos / Q000009:adverse effects* / Q000737:chemistry; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D007223:Infant; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology
D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D043182:Carboxylesterase; D004390:Chlorpyrifos