C. Chen et W. Nirunsuksiri, Decreased expression of glutathione S-transferase M1 in HPV16-transfected human cervical keratinocytes in culture, CARCINOGENE, 20(4), 1999, pp. 699-703
Glutathione S-transferase (GST) M1 is a member of the GST mu family of cyto
solic enzymes that have been hypothesized to catalyze the conjugation of gl
utathione to a large number of hydrophobic substances, including carcinogen
s such as polynuclear aromatic hydrocarbons present in tobacco smoke, leadi
ng to their excretion, Epidemiologic and experimental evidence suggests tha
t the risk of cervical cancer is related to both human papillomavirus (HPV)
infection and cigarette smoking. We compared the enzymatic activities and
mRNA levels of GSTs in GSTM1-positive human cervical keratinocytes (HCKs) t
hat had been transfected with HPV16 with those in the parental cells. The G
STM1 activity toward the substrate trans-stilbene oxide was 5- to 7-fold lo
wer than in the parental cells. The relative mRNA level in HCK transfected
with HPV16 E6/E7, as quantified by reverse transcriptase-polymerase chain r
eaction (RT-PCR) with normalization against endogenous glyceraldehyde-3-pho
sphate dehydrogenase (GAPDH) expression, was 6% that of the parental cells.
It was 16 and 82%, respectively, in cells that were transfected with HPV16
E6 alone or HPV16 E7 alone. When quantified by competitive RT-PCR using an
exogenous nuclease-resistant synthetic cyclophilin RNA transcript as contr
ol, the mRNA level in HCK transfected with HPV16 E6 was similar to 10-fold
lower that that in the parental cells, It was similar to 5- to 7-fold lower
in the HPV16 E7 or HPV16 E6/E7 cells, Our results suggest that viral infec
tions, through the modulation of cellular xenobiotic-metabolizing enzymes,
may play a role in the ability of cells to handle environmental carcinogens
.