Immunohistochemical detection of carcinogen-DNA adducts in normal human prostate tissues transplanted into the subcutis of athymic nude mice: Resultswith 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

Citation
L. Cui et al., Immunohistochemical detection of carcinogen-DNA adducts in normal human prostate tissues transplanted into the subcutis of athymic nude mice: Resultswith 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, JPN J CANC, 91(1), 2000, pp. 52-58
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
JAPANESE JOURNAL OF CANCER RESEARCH
ISSN journal
0910-5050 → ACNP
Volume
91
Issue
1
Year of publication
2000
Pages
52 - 58
Database
ISI
SICI code
0910-5050(200001)91:1<52:IDOCAI>2.0.ZU;2-6
Abstract
Human prostate tissue transplanted into nude mice was examined immunohistoc hemically for DNA adducts formed after administration of 3,2'-dimethyl-4-am inobiphenyl (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 tr anscription-polymerase chain reaction (RT-PCR) analysis revealed a normal h uman prostate epithelial cell line (PrEC) to express both cytochrome P450 I A2 (CYP1A2) and N-acetyltransferase 2 (NAT2) mRNA, while a normal human pro state fibroblast cell line (NHPF) expressed NAT2, but not CYP1A2 mRNA. In a ddition, NAT2 and to a lesser extent CYP1A2 mRNAs were also found in four c ases of normal human prostate tissues. The results suggest that initial act ivation of chemicals by liver CYP1A2 and subsequent metabolism by prostate NAT2 is a major pathway of DNA adduct formation in human prostate cells. Th us, the data suggest that human prostate has the potential to be targeted b y environmental carcinogens.