Prenatal exposure to a mixture of different phthalates increases the risk of mammary carcinogenesis in F1 female offspring

Author(s)

de Freitas, Thiago ^[1] ; Zapaterini, Joyce R. ^{[1, 2]} ; Moreira, Cristiane M. ^[1] ; de Aquino, Ariana M. ^[1] ; Alonso-Costa, Luiz G. ^[1] ; Bidinotto, Lucas T. ^{[3, 4, 2]} ; Kass, Laura ^[5] ; Flaws, Jodi A. ^[6] ; Scarano, Wellerson R. ^[1] ; Barbisan, Luis F. ^[1]

Affiliation

^[1] Sao Paulo State Univ, Inst Biosci, Dept Struct & Funct Biol, UNESP, Botucatu, SP - Brazil

^[2] Sao Paulo State Univ, UNESP, Sch Med, Dept Pathol, Sao Paulo, SP - Brazil

^[3] Barretos Canc Hosp, Mol Oncol Res Ctr, Barretos, SP - Brazil

^[4] Barretos Sch Hlth Sci, Dr Paulo Prata FACISB, Barretos, SP - Brazil

^[5] UNL CONICET, Inst Salud & Ambiente Litoral ISAL, Fac Bioquim & Ciencias Biol, Ciudad Univ UNL, Santa Fe - Argentina

^[6] Univ Illinois, Dept Comparat Biosci, Champaign, IL - USA

• Document type: Journal article
• Source: Food and Chemical Toxicology; v. 156, OCT 2021.
• Web of Science Citations: 0

Abstract

Phthalates metabolites have been detected in the urine of pregnant and breastfeeding women. Thus, this study evaluated the adverse effects of maternal exposure to a mixture of six phthalates (Pth mix) on the mammary gland development and carcinogenesis in F1 female offspring. Pregnant female Sprague-Dawley rats were exposed daily to vehicle or Pth mix (35.22% diethyl-phthalate, 21.03% di-(2-ethylhexyl)-phthalate, 14.91% dibutyl-phthalate, 15.10% diisononyl-phthalate, 8.61% diisobutyl-phthalate, and 5.13% benzylbutyl-phthalate) by gavage at 20 mu g/kg, 200 mu g/kg or 200 mg/kg during gestational day 10 (GD 10) to postnatal day 21 (PND 21). After weaning (PND 22), some female offspring were euthanized for mammary gland analyses while other females received a single dose of N-methyl-N-nitrosourea (MNU, 50 mg/kg) or vehicle and then tumor incidence and multiplicity were recorded until PND 180. Maternal Pth mix exposure increased the number of Ki-67 and progesterone receptor-positive epithelial cells in the mammary gland from Pth mix 200 at mu g/kg and 200 mg/kg groups. In addition, tumor incidence and mean number were higher only in Pth mix at 200 mg/kg when compared to the vehicle-treated group, and percentage of tumor-free animals was lower in Pth mix at 200 mu g/kg and 200 mg/kg groups. The findings indicate that perinatal Pth mixture exposure increased susceptibility to MNU-induced mammary carcinogenesis in adult F1 female offspring. (AU)

• FAPESP's process: 17/08306-2 - Oncotoxicological programming by the material exposure to the mixture of different fatalatos: multigenerational effect on prostate of rats and gene and epigenetic aspects related to prostate adenocarcinoma
• Grantee: Wellerson Rodrigo Scarano
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/50002-3 - A collaborative study between Brazilian and US scientists: the effects of environmental chemical exposures on reproduction
• Grantee: Wellerson Rodrigo Scarano
• Support Opportunities: Regular Research Grants