Expression of glutathione S-transferase and phenol sulfotransferase, but not of UDP-glucuronosyltransferase, in the human lung tumor cell lines NCI-H322 and NCI-H358.
The expression of xenobiotic-metabolizing enzymes was studied in the human lung tumour cell lines NCI-H322 and NCI-H358. These cells are derived from adenocarcinomas and exhibit features of Clara cells and alveolar type II cells, respectively. Examination of the in vitro activities showed that both cell lines lack UDP-glucuronosyltransferase against the substrates 3-hydroxybenzo[a]pyrene (3-OH-BaP) and 4-hydroxybiphenyl (4-OH-Bph) and that in vitro conjugation of sulfate with 3-OH-BaP was only just detectable. In contrast, both cell lines showed fairly high levels of glutathione-S transferase activity with the substrate 1-chloro-2,4-dinitro-benzene (54.4 and 83.0 nmol/min X mg protein, respectively) and of glutathione (81 and 41 nmole/mg protein, respectively). The metabolic capacity of intact NCI-H322 and NCI-H358 cells was examined using benzo[a]pyrene (BaP) and 3-OH-BaP as substrates. The cell lines formed sulfate conjugates from 3-OH-BaP (4.5 and 0.4 pmol/min X mg protein, respectively) but did not produce any detectable glucuronides. When cultures of the two cell lines were exposed to BaP, phenolic products accumulated in the growth medium. NCI-H322 cells also formed some sulfate conjugates, whereas such conjugates were barely detectable in the medium of NCI-H358 cells. In contrast A549, a human pulmonary adenocarcinoma cell line known to contain UDP-glucuronosyltransferase activity, efficiently conjugated 3-OH-BaP to glucuronic acid and converted the primary phenolic products formed from BaP to glucuronides. Thus the NCI-H322 and NCI-H358 cells are exceptional in that they possess no or very little glucuronosyltransferase activity but exhibit appreciable monooxygenase activity. The cell lines may therefore be of interest for examining the biological effects of potentially toxic chemicals which are otherwise detoxified by glucuronic acid conjugation. The cells may also be useful as test systems for evaluating the potential cytotoxicity and genotoxicity of chemicals to human lung.
Wiebel
F J
FJ
Kiefer
F
F
Krupski
G
G
Schuller
H M
HM
D015239:Arylsulfotransferase; D001564:Benzo(a)pyrene / Q000378:metabolism; D001580:Benzopyrenes / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005453:Fluorescence; D005965:Glucuronates / Q000378:metabolism; D005966:Glucuronidase / Q000032:analysis; D014453:Glucuronosyltransferase / Q000032:analysis*; D005982:Glutathione Transferase / Q000032:analysis*; D006801:Humans; D006900:Hydroxylation; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D010636:Phenols / Q000378:metabolism; D013466:Sulfurtransferases / Q000032:analysis*
D001580:Benzopyrenes; D005965:Glucuronates; D010636:Phenols; D001564:Benzo(a)pyrene; C021338:3-hydroxybenzo(a)pyrene; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D013466:Sulfurtransferases; D015239:Arylsulfotransferase; D005966:Glucuronidase