Tumorigenicity of nitrated derivatives of pyrene, benz[a]anthracene, chrysene and benzo[a]pyrene in the newborn mouse assay

Abstract

Eight nitropolycyclic aromatic hydrocarbons (PAHs), including 1- and 4-nitropyrene, 1,3-, 1,6- and 1,8-dinitropyrene, 7-nitrobenz[a]anthracene, 6-nitrochrysene and 6-nitrobenzo-[a]pyrene and their parent PAHs were tested fro tumorigenicity in the newborn mouse model by i.p. administration at 1, 8, and 15 days after birth. Both pyrene and 1-nitropyrene induced similar incidences of hepatic tumors in males, yielding a 12-15% and a 21-28% tumor incidence at total doses of 700 and 2800 nmol per mouse, respectively. Liver tumors did not occur in females and the 3-10% lung tumor yield in both sexes was similar to that found in solvent-treated controls. The presumed proximate carcinogen, 1-nitrosopyrene, administered at 700 nmol per mouse, caused liver tumors in 45% of the males and in 9% of the females. 4-Nitropyrene was more tumorigenic than pyrene or 1-nitropyrene; at a dose of 2800 nmol, it induced liver tumors in 83% of the males and 7% of the females, with a lung tumor yield of 38 and 31%, respectively. Female mice treated with 200 nmol of 1,3-, 1,6- or 1,8-dinitropyrene did not develop liver tumors but the hepatic tumor incidence in males was 20, 32 and 16%, respectively, which was significantly greater than that found in mice treated with pyrene. In male mice administered 2800 nmol of benz[a]anthracene, the hepatic tumor incidence was 79%, while treatment with 7-nitrobenz[a]anthracene showed an incidence of only 28%. Similarly, 560 nmol of benzo[a]pyrene caused a 49% liver tumor yield in males while those given 6-nitrobenzo[a]pyrene had a 28% incidence. Treatment with benzo[a]pyrene also induced a 35 and 48% lung tumor incidence in males and females while the comparable values in 6-nitrobenzo[a]pyrene-treated mice were 14 and 2%. Chrysene administered at 2800 nmol per mouse induced hepatic and lung tumors in 41% and 21% of the males, respectively; at the 700-nmol dose, it induced only liver tumors in 29% of the males and in none of the females. In contrast, treatment with 6-nitrochrysene at 700 nmol per mouse resulted in a 76 and 23% hepatic tumor incidence in males and females, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

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

“…These results are consistent with the metabolism studies in which more extensive reduction of 1-NOP than of 1-NP was observed. The facile reduction of 1-NOP followed by DNA binding in newborn mouse liver is also consistent with the results of the bioassay in which 1-NOP was more tumorigenic than 1-NP (21). These results support the role of N-dG-1-AP in liver tumorigenesis induced by 1-NOP in this model (21).…”

“…The facile reduction of 1-NOP followed by DNA binding in newborn mouse liver is also consistent with the results of the bioassay in which 1-NOP was more tumorigenic than 1-NP (21). These results support the role of N-dG-1-AP in liver tumorigenesis induced by 1-NOP in this model (21). The same adduct was also detected in newborn mouse lung following 1-NOP treatment; the amounts were slightly higher than those observed following 1-NP treatment.…”

Identification of mononitropyrenes and mononitrofluoranthenes in air particulate matter via fused silica gas, chromatography combined with negative ion atmospheric pressure ionization mass spectrometry

“…The possible atmospheric formation pathways of 4-NP and of the other mononitrofluoranthenes and mononitropyrenes are discussed elsewhere [30,31]. Additionally, this finding may have health implications since, although it is present in lower amounts, 4-NP is more tumorigenic than 1 -nitropyrene or pyrene [32].…”

Polycyclic Aromatic Hydrocarbons and Azaaromatic Compounds

“…Chrysene produced carcinomas and malignant lymphoma in mice after intraperitoneal injection and skin carcinomas in mice following dermal exposure (3). In later studies, the carcinogenicity of chrysene was assessed in three studies on newborn mice (208)(209)(210), in three initiation-promotion studies on mice (126,208,211) and after pulmonary implantation into rats (212). Chrysene gave a positive response in two of three assays in newborn mice, in one of three initiation-promotion studies and the pulmonary implantation study.…”