CARCINOGENESIS: Expression of cytochrome P450s and glutathione S-transferases in human esophagus with squamous-cell carcinomas

Abstract

In order to clarify the expression of cytochrome P450 and glutathione S-transferase in human esophagus, 41 samples of human esophagus with squamous-cell carcinoma were investigated by immunoblot analysis and enzyme assays. Cytochrome P450 1A2/1 was clearly expressed in microsomes, and the amount in samples with tumorous tissue was significantly greater than that in samples without tumourous tissues or in liver; cytochrome P450 2B6 and 3A4/3 were expressed polymorphically. Aryl hydrocarbon hydroxylase activity was detected in microsomes and was greater in samples from smokers than non-smokers. Patients who both smoked and drank alcohol, however, had activity similar to that of patients without these habits. Glutathione S-transferase M1 and A1/2 protein existed polymorphically in cytosol, and glutathione S-transferase P1-1 was detected in all samples. The frequency of expression of the glutathione S-transferase A1/2 protein was greater in patients with M1 protein than in those without; no difference in the expression was seen for glutathione S-transferase P1-1. Neither smoking nor drinking influenced the expression or activity of glutathione S-transferase. Our data support the idea that some carcinogens can be directly activated or inactivated in human esophageal epithelium.

Genetic polymorphisms of cytochrome P4501A1 and oesophageal squamous-cell carcinoma in Taiwan

“…Our findings approximate the Wang et al (2002) findings. Human cancers, e.g., gastrointestinal cancers, were suggested to be the result of the activation of procarcinogens into carcinogens (Nakajima et al, 1996). Murray et al (1994) and Nakajima et al (1996) examined the expression of cytochrome P450s in human esophagi with squamous-cell carcinomas.…”

“…Human cancers, e.g., gastrointestinal cancers, were suggested to be the result of the activation of procarcinogens into carcinogens (Nakajima et al, 1996). Murray et al (1994) and Nakajima et al (1996) examined the expression of cytochrome P450s in human esophagi with squamous-cell carcinomas. Both studies found that the amount of cytochrome P450 1A1 expression in tumorous tissue to be significantly higher than that in non-tumorous tissues.…”

Association of GSTP1 Polymorphism and Survival for Esophageal Cancer

“…GST activity is exhibited by a family of enzymes (a, A, k, j, and u). Enzyme activity can be detected in both normal and cancerous tissues of the esophagus and is not affected by cigarette smoking or alcohol consumption (11). In a report of one patient, complete tumor regression achieved by treatment with 5-fluorouracil plus cisplatin was found associated with the reduced tumor expression of GST-k (12).…”

Drug‐Metabolizing Enzymes and Transporters: Expression in the Human Prostate and Roles in Prostate Drug Disposition

“…Metabolism of carcinogens by CYPs has also been linked to initiation of cancer, for instance, in the esophagus (Murray et al, 1994b;Nakajima et al, 1996) and stomach (Murray et al, 1998), where CYP1B1 is overexpressed. The significance of CYP1B1 expression in prostate tumor cells, however, needs further scrutiny.…”