Smoking-related increase of O6-methylguanine-DNA methyltransferase expression in human lung carcinomas

Abstract

Eighty-three non-small cell lung carcinomas (NSCLC) of previously untreated patients were analysed for expression of O 6 -methylguanine-DNA methyltransferase (MGMT) by means of immunohistochemistry. Expression of MGMT was detected in 62 of 83 tumours (75%). There was a significant difference in MGMT staining between smokers and non-smokers (P ⍧ 0.001). Tumours of smokers expressed more frequently MGMT than tumours of nonsmokers. There was a trend of MGMT expression to be higher in tumours of patients smoking >20 cigarettes/day than patients smoking <20 cigarettes/day. Abstinence from smoking resulted in a significant decrease in MGMT expression (lin reg r ⍧ -0.59, P < 0.05). These results demonstrate that MGMT expression in human lung carcinomas is influenced by smoking habits of the patients.

The hypermethylation and protein expression of p16 INK4A and DNA repair gene O 6-methylguanine-DNA methyltransferase in various uterine cervical lesions

“…Several studies have demonstrated that the inactivation of a repair gene by promoter hypermethylation resulted in the impaired expression of MGMT protein [2,9,14,18,22]. The loss of protein was uniform in lymphoma, but tumors of the colon, lung, and brain showed cellular heterogeneity or stronger expression than adjacent normal tissues [14,23,27,36,41,49]. According to Kokkinakis et al [23], MGMT protein was absent in the hyperplastic and normal components of pancreatic tissues, but invariably present in dysplastic foci and especially strong in the invasive component of pancreatic cancer.…”

Inactivation of the DNA repair gene O6‐methylguanine‐DNA methyltransferase by promoter hypermethylation and its relationship to aflatoxin B1‐DNA adducts and p53 mutation in hepatocellular carcinoma

“…31,32 However, MGMT inactivation may be an early event in tumorigenesis conferring an increased susceptibility to nitrosamines and other alkylating agents. 15 It was previously demonstrated that cytosine methylation enhances guanine alkylation by a variety of bulky carcinogens (benzo(a)pyrene diol epoxide, AFB 1 8,9-epoxide, benzo(g)chrysene diol epoxide and N-acetoxy-2-acetylaminofluorene).…”

Protein expression profiles indicative for drug resistance of non-small cell lung cancer

“…In this analysis, several resistance proteins and additional resistancerelated factors were changed in resistant NSCLC in comparison to sensitive carcinomas. The reason for this concomitant expression of different factors may be the result of inducing a cascade of resistance-related gene products that can be triggered by environmental factors such as smoking (Volm et al, 1991Mattern et al, 1998). Another possible explanation is that lung cancer is mostly detected at a relatively late stage.…”