Development of Methods to Monitor Exposure to 1-Nitropyrene

Abstract

On the basis of 32P-postlabeling analysis, treatment of rats with 1-nitropyrene (1-NP) resulted in the formation of multiple DNA adducts in the liver, mammary glands, and peripheral lymphocytes. The one adduct resulting from nitroreduction, N-(deoxyguanosin-8-yl)-1-aminopyrene, constitutes only a minor component among the adducts. In the present study, incubation of calf thymus DNA with mutagenic ring-oxidized metabolites of 1-NP in vitro in the presence and absence of xanthine oxidase also resulted in the formation of multiple adducts. On the basis of their chromatographic behavior, it appears that DNA adducts derived from such metabolites may have been formed in vivo; however, this needs to be confirmed.[3H]1-NP was given to male and female F344 rats and Sprague-Dawley rats by gavage at five dose levels in the range of 0.1 to 1000 pg/kg bw. This led to stable hemoglobin adducts accounting for 0.08 ± 0.05% of the dose (n = 3 rats). The radioactivity associated with hemoglobin following administration of [3H]1-NP was cleared with a half-life of about 14 days, which is faster than that of unmodified erythrocytes in the rat (t1/2= 30 days).Treatment of the hemoglobin with 1% HCI in acetone, to precipitate the globin, released the radioactivity; it was all bound to the heme moiety. The structures of the heme adducts have not been elucidated; yet, because of their stability, they may be useful as dosimeters for human exposure to 1-NP. The results of this study demonstrate the potential of using hemoglobin adducts of 1-NP as dosimeters of uptake and metabolic activation of nitropolynuclear aromatic hydrocarbons (NO2-PAH). These indicators are a prerequisite for cancer risk assessment of N02-PAH. -Environ Health Perspect 102(Suppl 6): 31-37 (1994)

Identification of 5-(Deoxyguanosin-N2-yl)- 1,2-dihydroxy-1,2-dihydro-6-aminochrysene as the Major DNA Lesion in the Mammary Gland of Rats Treated with the Environmental Pollutant 6-Nitrochrysene

“…A number of ubiquitous environmental agents have been shown to induce mammary cancer in rodents; thus, they must be regarded as potential human risk factors and are candidates for a detailed evaluation. An example of such an environmental carcinogen is the class of nitropolycyclic aromatic hydrocarbons (NO 2 −PAHs) 1 ( − ), of which 6-nitrochrysene (6-NC) is a representative example. Factors such as the significant carcinogenic activity of 6-NC in the rat mammary gland, its environmental occurrence, the ability of human liver, lung, and breast tissue to convert 6-NC into DNA reactive metabolites, as well as the finding of its hemoglobin adducts in humans suggest that it likely contributes to the development of human breast cancer ( − ).…”

Study of the Interaction of Pollutant Nitro Polycyclic Aromatic Hydrocarbons with Different Metallic Surfaces by Surface-Enhanced Vibrational Spectroscopy (SERS and SEIR)

“…NPAHs can form adducts with DNA, inducing mutations in GC-rich sequences. − In addition, they can also interact with proteins. In the last case, the interaction has been reported to occur through the heme group of proteins, rather than with the peptidic group …”

“…In the last case, the interaction has been reported to occur through the heme group of proteins, rather than with the peptidic group. 9 The environmental importance of NPAHs, in relation to human health, leads us to develop new detection devices that are based on surface-enhanced vibrational spectroscopy (SEVS), toward the design and implementation of optical sensors based on SEVS.…”

Development of an Enzyme-Linked Immunosorbent Assay for 1-Nitropyrene

“…The anti-l-NP antibodies are being used in the preparation of sol-gel immunoadsorber material for quick and selective sample clean-up (34). Another interesting application of the 1-NP ELISA is the analyses of nitroarene protein and/or DNA adducts for human biomonitoring (35)(36)(37). The high potential of immunochemical methods for individual exposure measurements has been outlined recently (38).…”