Effects of exposure to benzophenone-3 on early molecular markers of mammary involution in HC11 cells

GOMEZ AL; BECKLEY MB; ALTAMIRANO GA; ODDI SL; SCHIERANO-MAROTTI G; MORALES-RUIZ T; MARTINEZ-MACIAS MI; MUÑOZ-DE-TORO M; ROLDÁN-ARJONA T; KASS L

Mar del Plata

Congreso; REUNION ANUAL DE SOCIEDADES DE BIOCIENCIAS 2023. LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2023

Sociedad Argentina de Investigación Clínica

Mammary involution is a period of intense tissue remodeling, and its alteration may result in inadequate lactation or predispose to tumor development. In this sense, the UV-filter benzophenone-3 (BP3) has been shown to have estrogenic activity and to alter apoptosis, which could affect this process. Here, we investigated whether exposure to BP3 modifies the expression of early molecular markers of involution in a murine mammary cell line. HC11 cells were grown to confluence and exposed to vehicle (0.1% ethanol) and 1 or 1000 nM of BP3 for 72 h. The cells were then differentiated with lactogenic hormones for another 72 h, after which the hormones were withdrawn. Cell viability was assessed immediately after BP3 exposure. Beta-casein (CSN2), Stat3, Bcl2 and Bax mRNA expression was analyzed at 0, 24, 48 and 72 h, whereas DNA methylation of Bcl2 and Bax promoters was assessed by bisulfite pyrosequencing at 24 h after removal of the lactogenic hormones. Cell viability and Stat3 mRNA expression were not affected by BP3 exposure. The exposure to BP3 1 nM increased the mRNA expression of CSN2 (11.9-fold), Bcl2 (5.3-fold) and Bax (1.5-fold) at 24 h, and reduced CSN2 expression (9.8-fold) at 72 h compared to vehicle. Bcl2 promoter showed reduced DNA methylation at 24 h in cells exposed to BP3 1 nM compared to vehicle, and no differences were observed in the Bax promoter. Our results showed that BP3 exposure could interfere with the normal involution of the mammary gland and modify the expression of key molecular markers of this process.