This paper is one of a series of papers in which, for a family L of graphs, we describe the typical structure of graphs not containing any L ∈ L. In this paper, we prove sharp results about the case L = {O6}, where O6 is the graph with 6 vertices and 12 edges, given by the edges of an octahedron. Among others, we prove the following results. (a) The vertex set of almost every O6-free graph can ...

Temozolomide is an alkylating agent used in the treatment of gliomas and, more recently, aggressive pituitary adenomas and carcinomas. Temozolomide methylates DNA and, thereby, has antitumor effects. O6-methylguanine-DNA methyltransferase, a DNA repair enzyme, removes the alkylating adducts that are induced by temozolomide, thereby counteracting its effects. A Medline search for all of the avai...

The rates of appearance and removal of 7-methylguanine and O6-methylguanine in DNA from rat liver, kidney, and colon were determined at various intervals up to 120 hr after i.p. administration of 10.2, 40.7, 81.5, or 163 mg 1,2-dimethylhydrazine (SDMH) per kg body weight (one-sixteenth, one-fourth, one-half, or one 50% lethal dose) using high-pressure liquid chromatography and fluorescence spec...

The kinetics of incorporation of deoxynucleotide precursors directed by the promutagenic base, O6-methylguanine (m6Gua), was analyzed during in vitro replication of m6Gua-containing synthetic polydeoxynucleotides by T4 and T5 phage DNA polymerases and Escherichia coli DNA polymerase I. When poly(dT,m6dG) and poly(dC,m6dG) with covalently attached primers were replicated, O6-methylguanine paired...

Chloroethylnitrosoureas (CENUs) are alkylating and crosslinking agents used for the treatment of human cancer; they are both mutagenic and carcinogenic. We compared the levels of induction of sister chromatid exchanges (SCEs) and the cytotoxicity of nitrosoureas that alkylate only with CENUs. CENUs are 200-fold more cytotoxic and induce SCEs with 45-fold greater efficiency than agents that do n...

Dideoxy chain-termination DNA sequencing was used to determine the specific DNA base changes induced after in vivo exposure of Escherichia coli to N-methyl-N-nitrosourea (MNU) and N-ethyl-N-nitrosourea (ENU) using the xanthine guanine phosphoribosyltransferase (gpt) gene as the genetic target. The resultant mutation spectra were compared with the levels of O6-alkylguanine and O4-alkylthymidine ...

Efficient in vivo selection increases survival of gene-corrected hematopoietic stem cells (HSCs) and protects hematopoiesis, even if initial gene transfer efficiency is low. Moreover, selection of a limited number of transduced HSCs lowers the number of cell clones at risk of gene activation by insertional mutagenesis. However, a limited clonal repertoire greatly increases the proliferation str...

The mutational specificity of the alkylating agent 1-3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) was analyzed at the endogenous hemizygous adenine phosphoribosyl transferase gene of the Chinese hamster ovary cell line D422. A 1-h treatment of the Chinese hamster ovary cells with 50 microM BCNU resulted in a toxicity level of 62% and induced mutation at this target with a frequency of 32.1 mutant...

We have examined the quantitative importance of various monosaccharide residues of an octasaccharide domain of heparin that are responsible for the binding of this oligosaccharide to antithrombin. Different fragments of the octasaccharide were prepared by enzymatic digestion and the avidities of these oligosaccharides for antithrombin were determined by equilibrium dialysis. The data show that ...