Immunohistochemical detection of carcinogen-DNA adducts in normal human prostate tissues transplanted into the subcutis of athymic nude mice: results with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 3,2'-dimethyl-4-aminobiphenyl (DMAB) and relation to cytochrome P450s and N-acetyltransferase activity.
Human prostate tissue transplanted into nude mice was examined immunohistochemically for DNA adducts formed after administration of 3,2'-dimethyl-4-aminobiphenyl (DMAB) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Positive staining for DMAB- or PhIP-DNA adducts was evident in 70-95% of both epithelial and stromal cells in human prostate xenografts. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed a normal human prostate epithelial cell line (PrEC) to express both cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 2 (NAT2) mRNA, while a normal human prostate fibroblast cell line (NHPF) expressed NAT2, but not CYP1A2 mRNA. In addition, NAT2 and to a lesser extent CYP1A2 mRNAs were also found in four cases of normal human prostate tissues. The results suggest that initial activation of chemicals by liver CYP1A2 and subsequent metabolism by prostate NAT2 is a major pathway of DNA adduct formation in human prostate cells. Thus, the data suggest that human prostate has the potential to be targeted by environmental carcinogens.
Cui
L
L
First Department of Pathology, Nagoya City University Medical School. cuilin@med.nagoya-cu.ac.jp
Takahashi
S
S
Tada
M
M
Kato
K
K
Yamada
Y
Y
Kohri
K
K
Shirai
T
T
D000368:Aged; D000611:Aminobiphenyl Compounds / Q000494:pharmacology*; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D018736:DNA Adducts / Q000032:analysis / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D011467:Prostate / Q000187:drug effects / Q000378:metabolism* / Q000637:transplantation; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000611:Aminobiphenyl Compounds; D002273:Carcinogens; D018736:DNA Adducts; D007093:Imidazoles; C001042:2',3-dimethyl-4-aminobiphenyl; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D019388:Cytochrome P-450 CYP1A2; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human