The 7-methylguanine adduct in the DNA of rat liver is determined as an indicator of exposure to exogenous and endogenous methylating agents. A method for the analysis of 7-methylguanine adducts has been developed by combining the selectivity of separation of reversed-phase HPLC with the specificity and high sensitivity of electrochemical detection. The sensitivity of the method is about 10,000-...

To study relations between increased transformation sensi tivity during DMA synthesis and carcinogen-induced molecular DMA alterations in regenerating liver, the kinetics of formation and the persistence of alkylated DMA bases were determined 10 to 240 min after a single [14C]dimethylnitrosamine (DMN) injection (1.43 and 4.0 mg/kg) during G, (12 h after partial hepatectomy) and in synchronized ...

The biosynthesis of tRNA was investigated in cultured astroglial cells and the 3-day-old rat brain in vivo. In the culture system astrocytes were grown for 19 days and were then exposed to [3H]guanosine for 1.5-7.5 h; 3-day-old rats were injected with [3H]guanosine and were killed 5-45 min later. [3H]tRNA was extracted, partially purified, and hydrolyzed to yield [3H]guanine and [3H]methyl guan...

Glioblastoma multiforme (GBM) is an extremely malignant type of primary brain tumor that exhibits a high mortality rate. Current standard therapy involves surgery followed by radiation and treatment with the DNA-alkylating agent, temozolomide (TMZ). While TMZ can extend post-operative survival, most patients develop resistance to which leads significant increase in mortality. At molecular level...

O(6)-Methylguanine produced in DNA can pair with thymine during DNA replication, thus leading to a G-to-A transition mutation. To prevent such outcomes, cells harboring O(6)-methylguanine-containing mispair undergo apoptosis that requires the function of mismatch repair (MMR) protein complex. To identify the genes involved in the induction of apoptosis, we performed gene-trap mutagenesis and is...

Mammary and skin tumors induced in rodents by N-methyl-N-nitrosourea treatment have a G:C to A:T transition mutation in codon 12 of H-ras, probably resulting from alkylation of O6 of guanine by the carcinogen. This codon contains two guanines (5'-GGA-3'), but mutations are observed only in the central base pair of this codon. The same selectivity for mutations of -GGA-sequences has also been ob...

It was found that rat kidney contains a protein similar to that previously described in rat liver which catalyzes the transfer of the methyl group from O6-methylguanine in DNA to a proteinbound cysteine residue. The amount of the renal O6-methylguanine-DNA methyltransferase was increased up to 2.5-fold during renal hypertrophy in response to unilateral nephrectomy or treatment with folie acid. ...

Primary Chinese hamster embryo cell cultures generally yield cell lines with a finite lifetime in culture. However, if early-passage cells are exposed chronically to either of two normal degradation products of transfer RNA, 1-methylguanine or 7-methylguanine, they are converted to con tinuous lines with altered growth characteristics and mor phology. The continuous cell lines have saturation d...

The ability of cloned human O6-methylguanine-DNA methyltransferase to repair a methylated guanine in a CpG-containing sequence, i.e., island, was studied by using a synthetic double-stranded 20-mer oligonucleotide from codon 248 of the p53 gene and another designed sequence. The double-stranded oligonucleotides incorporating 5-methylcytosine (5mC) and O6-methylguanine (O6mG) in various combinat...