Tumor initiating activities of 1-nitropyrene and its nitrated products in SENCAR mice

Nesnow, Stephen; Triplett, L. L.; Slaga, Thomas J.

doi:10.1016/0304-3835(84)90055-7

Cited by 23 publications

(8 citation statements)

References 12 publications

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“…Among the nitro-PAHs present in diesel exhaust that have been studied only 6-nitrochrysene exhibits a clear tumour initiating activity in mouse skin [59]. Dinitropyrenes showed a very weak carcinogenic activity [12] [59] were inactive in mouse skin.…”

Section: Discussionmentioning

confidence: 99%

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The genotoxic air pollutant 3-nitrobenzanthrone and its reactive metabolite N-hydroxy-3-aminobenzanthrone lack initiating and complete carcinogenic activity in NMRI mouse skin

et al. 2009

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Section: Discussionmentioning

confidence: 99%

“…ras) for carcinogenesis. The two-stage mouse skin carcinogenesis model has been used not only to examine the carcinogenic potential of single genotoxic agents [11,12] but also to evaluate the cancer risk of complex environmental mixtures such as cigarette smoke condensate, coal tar and diesel exhaust extracts [4,[13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

The genotoxic air pollutant 3-nitrobenzanthrone and its reactive metabolite N-hydroxy-3-aminobenzanthrone lack initiating and complete carcinogenic activity in NMRI mouse skin

et al. 2009

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“…1-NP causes malignant fibrous histocytomas at the site of injection and adenomas of the mammary gland in rats, as well as lung and liver tumors in mice (1S22). Like its parent hydrocarbon, pyrene, it had no apparent tumorigenic effect when painted on mouse skin (23,24). Although 1-NP induced mammary tumors in SpragueDawley rats, its reduced product, 1-NOP, was weakly active as a mammary carcinogen (20).…”

Section: Introductionmentioning

confidence: 98%

Metabolism and DNA binding of 1-nitropyrene and 1-nitrosopyrene in newborn mice

El‐Bayoumy

Shiue

Hecht

1988

Chem. Res. Toxicol.

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This study was carried out in order to evaluate possible mechanisms responsible for tumor induction by 1-nitropyrene and to provide insights on the higher tumorigenicity of 1-nitrosopyrene than 1-nitropyrene in newborn mouse liver. The "ground mouse" technique was used to follow the development of the metabolism of 1-nitropyrene and 1-nitrosopyrene in newborn and infant mice in vivo. Equimolar doses of 1-nitropyrene and 1-nitrosopyrene were used as in the bioassay reported previously. The compounds were administered by ip injection (100 nmol, day 1; 200 nmol, day 8; 400 nmol, day 15). The ethyl acetate soluble metabolites of 1-nitropyrene were identified as 1-aminopyrene, trans-4,5-dihydro-4,5-dihydroxy-1-nitropyrene, 1-nitropyren-3-ol, 1-nitropyren-6-ol, and 1-nitropyren-8-ol on the basis of cochromatography with synthetic standards in two different HPLC systems. Nitroreduction of 1-nitropyrene to 1-aminopyrene was observed only in 1 day old mice. Ethyl acetate soluble metabolites of 1-nitrosopyrene were identified as 1-aminopyrene and 1-nitropyrene. The capacity of 1 day old mice to metabolize 1-nitropyrene and 1-nitrosopyrene exceeded those of 8 and 15 day old mice. The extent of nitroreduction of 1-nitrosopyrene exceeded that of 1-nitropyrene. A major DNA adduct, N-(deoxyguanosin-8-yl)-1-aminopyrene, was identified and quantified in liver and in lung, 24 h after carcinogen treatment. The extents of formation of this adduct (pmol/mg of DNA, mean of two experiments) were as follows: 1-nitropyrene (liver, 4.1; lung, 1.2); 1-nitrosopyrene (liver, 30.4; lung, 6.3).(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Sources of these direct-acting mutagens are incomplete combustion processes and photochemical nitration of polycyclic aromatic hydrocarbons (PAHs) in the atmosphere (Pitts et al, 1978;Tokiwa et al, 1981). DNPs have been shown to be tumorigenic in rats, hamsters, and mice (Ohgaki et al, 1984(Ohgaki et al, , 1985Takayama et al, 1985;Wislocki et al, 19861, and to act as tumor initiators in mice (Nesnow et al, 1984). In addition, isomeric DNPs are genotoxic in yeast (Wilcox and Parry, 19811, mutagenic in V79, Chinese hamster ovary, and mouse lymphoma cells (Cole et al, 1982;Nakayasu et al, 1982;Li and Dutcher, 1983;Heflich et al, 1986;Fifer et al, 19861, and induce single-strand breaks (Saito et al, 1984) and cytogenetic alterations (Nachtman and Wolff, 1982;Danford et al, 1982;DiPaolo et al, 1983).…”

Section: Introductionmentioning

confidence: 99%

Metabolism of 1,8‐dinitropyrene by human, rhesus monkey, and rat intestinal microflora

Cerniglia

Lambert

White

et al. 1988

Environ. Toxicol. Water Qual.

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Dinitropyrenes (DNPs) are highly mutagenic in the Salmonella reversion assay and are tumorigenic in rodents. Bacterial nitroreductases have been implicated in the mutagenic activation of DNPs. In this study, we investigated the metabolism of 1,8‐dinitropyrene (1,8‐DNP) by anaerobic bacterial suspensions derived from human feces, and the intestinal contents of rhesus monkeys and rats. The 1,8‐DNP metabolites were isolated by reversed‐phase high performance liquid chromatography, and identified by comparison of their chromatographic and mass spectral properties with those of authentic compounds. All of the intestinal microflora metabolized 1,8‐DNP to 1‐amino‐8‐nitropyrene and 1,8‐diaminopyrene. The mutagenic activity of samples extracted from incubations of human or rat intestinal microflora cultured with 1,8‐DNP was measured by reversion of Salmonella typhimurium TA98. There was a decrease in the mutagenic activities of the extracts with time of incubation that correlated with increased 1‐amino‐8‐nitropyrene and 1,8‐diaminopyrene formation. The decreased mutagenicity of the 1,8‐DNP metabolites was confirmed by conducting assays with authentic 1‐amino‐8‐nitropyrene and 1,8‐diaminopyrene. Both compounds showed much lower mutagenic activity compared to 1,8‐DNP. The results indicate that intestinal microflora have the ability to metabolize 1,8‐DNP to amine derivatives that are less mutagenic than the parent compound.

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Tumor initiating activities of 1-nitropyrene and its nitrated products in SENCAR mice

Cited by 23 publications

References 12 publications

The genotoxic air pollutant 3-nitrobenzanthrone and its reactive metabolite N-hydroxy-3-aminobenzanthrone lack initiating and complete carcinogenic activity in NMRI mouse skin

The genotoxic air pollutant 3-nitrobenzanthrone and its reactive metabolite N-hydroxy-3-aminobenzanthrone lack initiating and complete carcinogenic activity in NMRI mouse skin

Metabolism and DNA binding of 1-nitropyrene and 1-nitrosopyrene in newborn mice

Metabolism of 1,8‐dinitropyrene by human, rhesus monkey, and rat intestinal microflora

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