Disease relevance of CCRIS 2586

• One strain had a normal capacity for nucleotide excision repair, the second exhibited an intermediate rate of repair, and the third, derived from a patient with xeroderma pigmentosum, had no ability to repair UV- or 1-nitrosopyrene-induced DNA damage [1].
• Percentages of incidences of mammary adenocarcinomas in female rats were as follows: 1-nitropyrene, high dose (63%); 1-nitropyrene, low dose (42%); 1-nitrosopyrene (19%); 1-aminopyrene (4%) trioctanoin (3%) [2].
• In Salmonella the limiting step in the metabolic activation of 1-nitropyrene appears to be the initial reduction to 1-nitrosopyrene, while with the dinitropyrenes subsequent esterification of the reduced intermediates seems critical [3].
• These data indicate that a limiting step in the cellular toxicity and transformation of normal human diploid fibroblasts by 1-nitropyrene is the initial reduction to 1-nitrosopyrene [4].
• The mutagenicity of 1-nitropyrene and its reduced metabolite 1-nitrosopyrene was determined in the lambda cI gene of an Escherichia coli uvr- lysogen [5].

High impact information on CCRIS 2586

• Site-specific excision repair of 1-nitrosopyrene-induced DNA adducts at the nucleotide level in the HPRT gene of human fibroblasts: effect of adduct conformation on the pattern of site-specific repair [6].
• To see if site-specific DNA repair is a common phenomenon for bulky DNA adducts, we determined the rate of repair of 1-nitrosopyrene (1-NOP)-induced adducts in exon 3 of the hypoxanthine phosphoribosyltransferase gene at the nucleotide level using ligation-mediated PCR [6].
• Kinds and spectrum of mutations induced by 1-nitrosopyrene adducts during plasmid replication in human cells [7].
• Comparative tumorigenicity of 1-nitropyrene, 1-nitrosopyrene, and 1-aminopyrene administered by gavage to Sprague-Dawley rats [2].
• The results indicate a specificity for the induction of mutations in the hprt gene of CHO cells by 1-nitrosopyrene with respect to both the types of mutations produced and their location in the hprt gene [8].

Chemical compound and disease context of CCRIS 2586

• When the reducer column was introduced just after the separation column, 1-NP, 1-nitrosopyrene and 1-aminopyrene in the incubation mixture of 1-NP and the Salmonella typhimurium YG1021 strain were separately determined with detection limits as low as sub fmol levels [9].

Biological context of CCRIS 2586

• Effect of nucleotide excision repair in human cells on intrachromosomal homologous recombination induced by UV and 1-nitrosopyrene [1].
• Treatment of normal human diploid fibroblasts with 0.3-22 microM 1-nitrosopyrene resulted in a dose-dependent decrease in relative cloning efficiency and an increase in anchorage-independent growth in soft agar [4].
• DNA sequence analysis of 1-nitrosopyrene-induced mutations in the hprt gene of Chinese hamster ovary cells [8].
• Using polymerase chain reaction amplification of cDNA synthesized from RNA, the hprt protein-coding region could be amplified from 23 of the 1-nitrosopyrene-induced mutants and 11 of the control mutants [10].
• Chinese hamster ovary cells were exposed to N-hydroxy-2-aminofluorene, N-hydroxy-N'-acetylbenzidine and 1-nitrosopyrene, and the resulting DNA adducts, sister-chromatid exchanges (SCEs) and mutations at the hypoxanthine-guanine phosphoribosyl transferase locus were quantified [11].

Anatomical context of CCRIS 2586

• Kinds and locations of mutations induced in the hypoxanthine-guanine phosphoribosyltransferase gene of human T-lymphocytes by 1-nitrosopyrene, including those caused by V(D)J recombinase [12].
• When incubations were conducted with rat liver cytosol, only the reduced products 1-nitrosopyrene and 1-aminopyrene were detected [13].
• The two N2-deoxyguanosinyl adducts were also identified in an ascorbic acid-catalyzed activation of 1-nitrosopyrene and in the mammary gland of female Sprague-Dawley rats administered 1-nitropyrene [14].
• The major DNA adduct produced by 1-nitropyrene and 1-nitrosopyrene in calf thymus DNA co-migrated on h.p.l.c., and the structure was consistent with that previously described by others as N-(deoxyguanosin-8-yl)-1-aminopyrene [15].

Associations of CCRIS 2586 with other chemical compounds

• Since reduction of 1-nitrosopyrene was necessary to get appreciable DNA binding in vitro, further reduction of 1-nitrosopyrene to N-hydroxy-1-aminopyrene is probably required in the activation pathway [16].
• A single DNA adduct, N-(deoxyguanosin-8-yl)-1-aminopyrene, is produced in CHO cells treated with 1-nitrosopyrene, and this adduct is found in rats and mice exposed to 1-nitropyrene [10].
• Relationships between the DNA adducts and the mutations and sister-chromatid exchanges produced in Chinese hamster ovary cells by N-hydroxy-2-aminofluorene, N-hydroxy-N'-acetylbenzidine and 1-nitrosopyrene [11].
• 1-Nitropyrene (5.2 pmol/mg DNA/h) and 1-nitrosopyrene (129 pmol/mg DNA/h) formed a single DNA adduct in Chinese hamster lung cells which co-eluted on h.p.l.c. with the C-8 deoxyguanosine adduct isolated from 1-nitropyrene-treated calf thymus DNA [15].

Gene context of CCRIS 2586

• In order to determine how this initial premutational lesion is converted to a stable heritable mutation, DNA sequences were determined for 30 mutations induced by 1-nitrosopyrene that mapped between bp 1 and 352 in the lambda cI gene of E.coli lysogens [5].

Analytical, diagnostic and therapeutic context of CCRIS 2586

• Analysis of solvent control and 1-nitrosopyrene-induced Chinese hamster ovary cell mutants by Southern and northern blots and the polymerase chain reaction [10].
• Female BALB/c and AJ mice were also immunized with 1-nitrosopyrene-modified KLH and 4 out of 18 surviving animals produced a low titer response when measured by an [3H] acetylaminopyrene-based radioimmunoassay [17].

References