Activity of nitro‐polynuclear aromatic hydrocarbons in the sister chromatid exchange assay with and without metabolic activation

Nachtman, J. P.; Wolff, Sheldon M.

doi:10.1002/em.2860040102

Cited by 71 publications

(13 citation statements)

References 17 publications

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“…However, 1-nitropyrene does induce sister-chromatid exchanges in CHO cells (23), transforms cultured mammalian cells (24,25), and is carcinogenic in rats (26,27). It is not clear whether 1-nitropyrene is a poor mutagen in mammalian cells because it produces no mutagenic DNA damage or because the genetic loci assayed are insensitive to the damage it produces.…”

Section: Introductionmentioning

confidence: 99%

DNA adduct formation and mutation induction by nitropyrenes in Salmonella and Chinese hamster ovary cells: relationships with nitroreduction and acetylation.

Heflich¹,

Fifer²,

Djurić³

et al. 1985

Environ Health Perspect

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Nitrated pyrenes are environmental pollutants and potent mutagens in the Salmonella reversion assay. In this study reversion induction by 1-nitropyrene and 1,8-dinitropyrene in Salmonella typhimurium TA1538 and mutation induction by 1-nitropyrene in Chinese hamster ovary (CHO) cells were related to the extent of metabolism and DNA adduct formation. In suspension cultures of Salmonella typhimurium TA1538, 1,8-dinitropyrene was up to 40-fold more mutagenic than 1-nitropyrene, although both compounds were metabolized at similar rates with nitroreduction being the major pathway. The major metabolite formed from 1-nitropyrene after 2 hr of incubation was 1-nitrosopyrene, while 1-amino-8-nitropyrene was the major metabolite formed from 1,8-dinitropyrene. 1-Nitrosopyrene and 1-nitro-8-nitrosopyrene elicited mutation values consistent with their being intermediates in the activation pathways. However, subsequent to nitroreduction, 1,8-dinitropyrene appeared to be further activated by acetylation, while 1-nitropyrene was not. Each nitrated pyrene produced a major DNA adduct substituted at the C8-position of deoxyguanosine. Although 1,8-dinitropyrene was more mutagenic than 1-nitropyrene, both compounds induced a similar number of revertants per adduct. Incubation of 1-nitrosopyrene with CHO cells produced a rapid concentration-and time-dependent induction of mutations and the conversion of 1-nitrosopyrene to 1-aminopyrene. In contrast, 1-nitropyrene did not induce mutations and was not converted to 1-aminopyrene. Both compounds produced the same major adduct, but adduct formation by 1-nitropyrene was much lower than by 1-nitrosopyrene. These data indicate that nitroreduction and C8 deoxyguanosine adduct formation are strongly associated with mutation induction by 1-nitropyrene in Salmonella and CHO cells. With 1,8-dinitropyrene, however, mutation induction in Salmonella is dependent upon both nitroreduction and esterification

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Section: Introductionmentioning

confidence: 99%

DNA adduct formation and mutation induction by nitropyrenes in Salmonella and Chinese hamster ovary cells: relationships with nitroreduction and acetylation.

Heflich¹,

Fifer²,

Djurić³

et al. 1985

Environ Health Perspect

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“…Although 1-nitropyrene has been considered a ques-tionable "direct-acting" mutagen in mammalian cells (59), it has been shown to induce sister chromatid exchanges in Chinese hamster ovary cells (60,61) and to transform cultured mammalian cells (62,63). Dinitropyrenes (e.g., 1,6-and 1,8-dinitropyrenes) have been shown to be among the most powerful mutagens ever tested (as assayed in S. typhimurium TA 98) (19,64).…”

Section: Nitropolynuclear Aromatic Hydrocarbonsmentioning

confidence: 99%

Contribution of organic particulates to respiratory cancer.

Matanoski¹,

Fishbein

Redmond

et al. 1986

Environ Health Perspect

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This paper presents some of the issues that remain to be resolved in order to assess the risk of cancer related to exposure to organic particulates. Most reviews of the effects of organic particulates from the outdoor environment on the risk of lung cancer show that this source seems to play a minor role. However, as fuel use and chemical composition of air pollutants change, the contribution of outdoor pollution as a cause of cancer may also change. Indoor air pollution is a more important source of exposure to organic particulates than is outdoor exposure. Although there is clear evidence that in occupational settings organic particulates cause human cancer, there has been almost no study of exposure to these types of particulates within indoor settings. Previous research has focused on cigarette smoke as the major indoor pollutant, but more specific characterization of contaminants in both the workplace and the home is required. The health effects of the higher levels of some of these contaminants in the workplace should be evaluated and the results extrapolated to populations exposed to lower levels in the home. Extensive research is needed to characterize organic particulate mixtures appropriately and test them for carcinogenicity. Studies on the health risks of nitropolynuclear aromatic hydrocarbons and polychlorinated dibenzodioxins and dibenzofurans are reviewed, but their contribution to the overall burden of respiratory cancer in humans cannot be estimated at this time. Characterization of mixtures, assessment of exposures, and linkage of exposures to health effects are the objectives of the recommendations proposed for further research.

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“…After incubation, the attached macrophages were detached by trypsinization and recovered by centrifugation at 300g, then lysed with 25 mL lysing buffer (50 mM Tris-HCl, 10 mM EDTA, 1% SDS, pH 8.0). The lung or tracheal tissues were separated from the culture medium by filtration through nylon mesh, then homogenized in 20 mL of the lysing buffer.…”

Section: In Vitro Tissue Preparation and Incubationmentioning

confidence: 99%

“…Nitro-substituted PAHs (NO2-PAH) have been found in extracts from diesel particles (2)(3)(4)(5) and ambient air particulates (6). Many of these NO2-PAH are mutagenic in mammalian cells (7)(8)(9)(10) as well as in bacteria (8)(9)(10)(11)(12) and may, therefore, be a potential risk to human health.…”

Section: Introductionmentioning

confidence: 99%

Nitropyrene: DNA Binding and Adduct Formation in Respiratory Tissues

Jackson¹,

King²,

Ball³

et al. 1985

Environmental Health Perspectives

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Binding of 1-nitro (14C)pyrene (NP) or its metabolites to cellular DNA and protein in cultures of rabbit alveolar macrophages, lung tissue, and tracheal tissue was examined. DNA binding in tracheal tissue (136 + 18.3 pmole NP/mg DNA) was four to five times the levels measured in either lung tissue (38 ± 9.4 pmole NP/mg DNA) or macrophages (26 ± 7.5 pmole NP/mg DNA). Adduct analysis of DNA isolated from lung tissue incubated with 1-nitro[H3]pyrene in vitro resulted in the identification of 2 to 5% of the NP adducts as C8-deoxyguanosine 1-aminopyrene. NP was also bound to cellular protein in tracheal tissue and lung tissue, and at a lower level in macrophages. Cocultivation of the macrophages with lung and tracheal tissue decreased the DNA binding in tracheal tissue by 45%. Following intratracheal instillation of diesel particles (5 mg) vapor-coated with "C-NP (380 ppm, 0.085 p.Ci/mg) particles into rats, 5-8% of the radioactivity remained in the lungs after 20 hr. Most of the diesel particles were also deposited in the lung. Examination of DNA and protein binding in this tissue showed 5 to 12% of the pulmonary "C bound to protein and no detectable levels of 14C bound to DNA.

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Activity of nitro‐polynuclear aromatic hydrocarbons in the sister chromatid exchange assay with and without metabolic activation

Cited by 71 publications

References 17 publications

DNA adduct formation and mutation induction by nitropyrenes in Salmonella and Chinese hamster ovary cells: relationships with nitroreduction and acetylation.

DNA adduct formation and mutation induction by nitropyrenes in Salmonella and Chinese hamster ovary cells: relationships with nitroreduction and acetylation.

Contribution of organic particulates to respiratory cancer.

Nitropyrene: DNA Binding and Adduct Formation in Respiratory Tissues

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