The effects of phénobarbital(PB) and other liver monooxygenase modifiers on dimethylnitrosamine (DMN)-induced alkylation of rat liver DNA and protein were investigated at different carcin ogen doses. In rats given single injections of radioactively labeled DMN, pretreatment with PB (80 mg/kg body weight, adminis tered for 5 days) resulted in a small but significant decrease in the formation of...

Comparison of the conformational stability of an O(6)-methylguanine-DNA methyltransferase (MGMT) from the hyperthermophilic archaeon Thermococcus kodakaraensis strain KOD1 (Tk-MGMT), and its mesophilic counterpart C-terminal Ada protein from Escherichia coli (Ec-AdaC) was performed in order to obtain information about the relationship between thermal stability and other factors, such as thermod...

Temozolomide (TMZ) is a DNA methylating agent used to treat brain cancer. TMZ-induced O6-methylguanine adducts, in the absence of repair by O6-methylguanine DNA methyltransferase (MGMT), mispair during DNA replication and trigger cycles of futile mismatch repair (MMR). Futile MMR in turn leads to the formation of DNA single and double strand breaks, Chk1 and Chk2 phosphorylation/activation, cel...

Isocitrate dehydrogenase 1 gene mutations are found in most World Health Organization grade II and III gliomas and secondary glioblastomas. Isocitrate dehydrogenase 1 mutations are known to have prognostic value in high-grade gliomas. However, their prognostic significance in low-grade gliomas remains controversial. We determined the predictive and prognostic value of isocitrate dehydrogenase 1...

The wide variation in the world-wide incidence of esophageal carcinoma suggests that environmental agents including chem icals cause this cancer. Since the interaction between chemical procarcinogens and human esophagus has not been studied previously, we examined the metabolic fate of benzo(a)pyrene (BP), N-nitrosodimethylamine (DMN), and A/-nitrosopyrrolidine in cultured nontumorous esophagus...

Incubation of 3-day-old rat brain with L-[methyl-3H]methionine resulted in the rapid labeling of low-molecular-weight cytoplasmic RNA. Electrophoresis in 15% polyacrylamide gels provided evidence for the methylation of precursor tRNA molecules, and high-performance liquid chromatography demonstrated N2-methylguanine to be the predominant methylated base formed during the first 2 min of labelling.