Determination of whole mixture-based potency factors for cancer risk assessment of complex environmental mixtures by in vitro testing of standard reference materials

Mining Potential Drug Targets for Osteoporosis Based on CeRNA Network

“…Related studies had shown that polycyclic aromatic hydrocarbons were associated with cancer, immunosuppression, decreased resistance to viral and bacterial infections, and decreased endocrine function. 52 , 53 , 54 , 55 BaP could also inhibit osteoclast formation and bone resorption by binding to aryl hydrocarbon receptor (Ahr), which related to the inhibition of RANKL signal pathway. 56 , 57 Moreover, studies demonstrated BaP inhibited TGF‐β1/SMAD4 and TGF‐β1/ERK/AKT signaling pathways by activating Ahr, thus inhibiting the osteogenic differentiation of BMSC.…”

“…Benzo[a]pyrene (BaP) is a typical polycyclic aromatic hydrocarbon, which usually exists in cigarette smoke and smog. Related studies had shown that polycyclic aromatic hydrocarbons were associated with cancer, immunosuppression, decreased resistance to viral and bacterial infections, and decreased endocrine function 52–55 . BaP could also inhibit osteoclast formation and bone resorption by binding to aryl hydrocarbon receptor (Ahr), which related to the inhibition of RANKL signal pathway 56,57 .…”

Lung cancer associated with combustion particles and fine particulate matter (PM2.5) - The roles of polycyclic aromatic hydrocarbons (PAHs) and the aryl hydrocarbon receptor (AhR)

“…As an alternative to genotoxicity testing of PM, the levels of PAHs in organic extracts from combustion PM can be also combined with information of the specific carcinogenic or AhR potencies of PAHs based on in vivo and/or in vitro data [ 134 , 137 , 150 ]. Other carcinogenicity-linked endpoints have been also proposed to quantify relative carcinogenic potencies of PAHs [ 26 , 151 ] Carcinogenicity risk assessment of PAHs is often based on toxic equivalency factors (TEFs) expressed relative to B[ a ]P, based on meta -analysis of animal carcinogenicity studies, as proposed by Nisbet and LaGoy [ 150 ], which serve to derive carcinogenicity of mixtures of PAHs, where an individual PAH concentration is multiplied by its respective TEF [ 152 153 ]. Such approach may serve to identify principal contributors of carcinogenicity or specific toxic action of PAH mixtures, and it has suggested that cyclopenta[ c,d ]pyrene, in addition to B[ a ]P, could be a prominent contributor to the estimated mutagenicity of the PAHs found in combustion PM samples [ 154 , 155 ].…”

Impacto da queima de biomassa na concentração de compostos policíclicos aromáticos e na toxicidade >i<in vitro>/i< do material particulado atmosférico de Ribeirão Preto-SP

“…Outra limitação desta abordagem é relacionada à disparidade encontrada entre os valores de TEF ou RPF para os HPA individuais, além do fato que há muitos HPA que ainda não tiveram a atribuição de um fator relativo (JARVIS et al, 2014). Recentemente uma abordagem baseada na avaliação da mistura complexa como um todo, para determinar fatores potencias de mistura (mixture potency factors -MPF) foi proposto, empregando um modelo in vitro a partir da resposta ao dano no DNA observado em células HepG2, evitando assim o uso de experimentos com animais GALVÃO et al, 2022). As células hepáticas do tipo HepG2 foram escolhidas pois contêm muitas das enzimas funcionais envolvidas no metabolismo de várias substâncias químicas tóxicas, incluindo dos HPA .…”

“…Neste modelo, a resposta é monitorada pela concentração da quinase Chk1 e da histona variante H2AX ativadas. Esse modelo pode inclusive ser utilizado para calcular os valores de TEF ou RPF para os HPA individuais, sendo que apresentou uma ótima correspondência com os valores obtidos com ensaios in vivo já publicados anteriormente GALVÃO et al, 2022). Um exemplo de HPA que não possui um valor de TEF ou RPF atribuído é o reteno, um alquil-HPA emitido principalmente pela queima de biomassa.…”