CHARACTERIZATION OF XENOBIOTIC-METABOLIZING ENZYME EXPRESSION IN HUMAN BRONCHIAL-MUCOSA AND PERIPHERAL LUNG TISSUES

The human respiratory epithelium is in direct contact with chemical ca rcinogens and toxins in inhaled air. Therefore, the activities of xeno biotic-metabolising enzymes in this epithelium could modulate respirat ory toxicity and carcinogenesis. We determined the expression of sever al xenobiotic-metabolising enzymes, including phase I and phase II enz ymes, in human bronchial mucosa and peripheral lung tissues. Reverse t ranscription-polymerase chain reaction (RT-P CR) analysis of phase I e nzymes showed CYP1A1 and CYP2C (CYP2C8 and CYP2C18) mRNA expression in all of the 14 bronchial mucosa specimens. CYP2A6 and CYP2B6 mRNAs wer e found in 85% of the samples, whereas 50 and 90% of the tissues displ ayed CYP2E1 and CYP3A5 expression, respectively. However, CYP1A2, CYP2 D6 and CYP3A4 mRNAs were not detected in all samples analysed. Normal human bronchial epithelial cells (NHBE cells) cultured in serum-free c onditions showed reduced P450 expression in comparison with the bronch ial mucosal samples. Similar to the bronchial mucosa, the peripheral l ung tissues expressed CYP1A1, CYP2A6, CYP2B6, CYP2C (CYP2C8 and CYP2C1 8), CYP2E1 and CYP3A5 mRNAs, but did not show detectable levels of CYP 2D6. Additional P450s, such as CYP1A2 and CYP3A4, were detected. The e xpression of CYP1A1, CYP1A2, CYP2B6, CYP2E1 and CYP3A4/5 in peripheral lung tissues was confirmed at the protein level, whereas CYP2A6 prote in was undetectable. The use of specific primers for the detection of the phase II isoenzymes belonging to the glutathione S-transferase mu (GST mu) and N-acetyl transferase (NAT) families showed that GSTM1 was expressed in 40% of the bronchial mucosa and 25% of the peripheral lu ng tissues, whereas GSTM3 and NAT1 mRNAs were found in all bronchial a nd lung samples. Finally, NAT2 expression was detected in all peripher al lung tissues, but was not detected in the bronchus. In conclusion, these results describing the diversity of the xenobiotic-metabolising enzymes expressed in the bronchus and lung tissues indicate that the h uman respiratory system could significantly and specifically contribut e to the activation and metabolism of several environmental procarcino gens. (C) 1998 Elsevier Science Ltd. All rights reserved.