N-Acetyltransferase and sulfotransferase activity in human prostate: potential for carcinogen activation.
BACKGROUND
N-Acetyltransferases (NATs) and sulfotransferases (SULTs) are key phase II metabolizing enzymes that can be involved both in the detoxification and in the activation of many human promutagens and procarcinogens.


RESULTS
We investigated the expression of NATs and SULTs in human prostate and tested their role in the activation the N-hydroxy (N-OH) metabolite of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a dietary carcinogen, to form DNA adducts. Western blotting showed detectable levels of NAT1, SULT1A1 and SULT1A3 with marked inter-individual variation. NAT2 and other SULT enzymes were not detectable. NAT1 was localized by immunohistochemistry to the cytoplasm of epithelial cells. The presence of acetyl Co-enzyme A (acetyl CoA) and 3'-phosphoadenosine-5'-phosphosulfate (PAPS), NAT and SULT cofactors, respectively, significantly increased the level of DNA adducts, detected by P-postlabelling analysis, in calf thymus DNA incubated with N-OH-IQ and prostate cytosolic fractions. The enhancement in the level of DNA adducts in the presence of PAPS correlated with the level of SULT1A1 protein. A single prostate cytosol with the SULT1A1*2/*2 genotype produced less DNA adducts than cytosols with the *1/*2 and *1/*1 genotypes. No significant correlation was observed between NAT1 protein level and the formation of DNA adducts, even in the presence of acetyl CoA.


CONCLUSIONS
In conclusion, we demonstrated that NAT1, SULT1A1 and SULT1A3 are present in human prostate and that both enzyme classes significantly contribute to the activation of N-hydroxylated heterocyclic amines to DNA-damaging species in this tissue. Variation in expression levels, in combination with dietary and/or environmental exposure to carcinogens, could be influential in determining individual susceptibility to prostate cancer.
Al-Buheissi
Salah Z
SZ
Institute of Cancer Research, Section of Molecular Carcinogenesis, Sutton, UK. salbuheissi@aol.com
Patel
Hiten R
HR
Meinl
Walter
W
Hewer
Alan
A
Bryan
Richard L
RL
Glatt
Hansruedi
H
Miller
Ronald A
RA
Phillips
David H
DH
D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000032:analysis / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism*; D008297:Male; D011467:Prostate / Q000166:cytology / Q000201:enzymology*; D015238:Sulfotransferases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
D002273:Carcinogens; D018736:DNA Adducts; D007527:Isoenzymes; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; D015238:Sulfotransferases