Tr. Fennell et al., Hemoglobin adducts from acrylonitrile and ethylene oxide in cigarette smokers: Effects of glutathione S-transferase T1-null and M1-null genotypes, CANC EPID B, 9(7), 2000, pp. 705-712
Acrylonitrile (ACN) is used to manufacture plastics and fibers. It is carci
nogenic in rats and is found in cigarette smoke. Ethylene oxide (EO) is a m
etabolite of ethylene, also found in cigarette smoke, and is carcinogenic i
n rodents. Both ACN and EO undergo conjugation with glutathione, The object
ives of this study were to examine the relationship between cigarette smoki
ng and hemoglobin adducts derived from ACN and EO and to investigate whethe
r null genotypes for glutathione transferase (GSTM1 and GSTT1) alter the in
ternal dose of these agents. The hemoglobin adducts N-(2-cyanoethyl)valine
(CEVal), which is formed from ACN, and N-(2-hydroxyethyl)valine (HEVal), wh
ich is formed from EO, and GST genotypes were determined in blood samples o
btained from 16 nonsmokers and 32 smokers tone to two packs/day), Smoking i
nformation was obtained by questionnaire, and plasma cotinine levels were d
etermined by immunoassay, Glutathione transferase null genotypes (GSTM1 and
GSTT1 were determined by PCR, Both CEVal and HEVal levels increased with i
ncreased cigarette smoking dose (both self-reported and cotinine-based), CE
Val and HEVal levels mere also correlated, GSTM1 and GSTT1 genotypes had li
ttle effect on CEVal concentrations. GSTM1 null genotypes had no significan
t impact on HEVal. However, HEVal levels mere significantly elevated in GST
T1-null individuals when normalized to smoking status or cotinine levels. T
he ratio of HEVal:CEVal was also elevated in GSTT1-null smokers (1.50 +/- 0
.57 versus 0.88 +/- 0.24; P = 0.0002). The lack of a functional GSTT1 is es
timated to increase the internal dose of EO derived from cigarette smoke by
50-70%.