Abstract A48: Perinatal DDT exposure shortens latency of mouse mammary tumorigenesis

The contribution of exposure to the persistent, lipophilic pesticide dichlorodiphenyltrichloroethane (DDT) to breast cancer risk is controversial. A recent report by the International Agency for Research on Cancer (IARC) concluded that no consistent association exists between DDT exposure and breast cancer, yet stressed that there was a lack of existing evidence to allow for the determination of the effects of early-life exposure to DDT. It has been hypothesized that exposure to DDT during critical periods of breast development may increase breast cancer risk. We hypothesized that perinatal DDT exposure would result in shortened latency of spontaneous mammary tumorigenesis and accelerated growth of mammary tumors and increase the incidence of lung metastasis. To test the effect on mammary tumor early progression and growth as well as lung metastasis, C57BL/6J female mice, pregnant as a result of mating with B6.FVB-Tg(MMTV-PyVT)634Mul/LellJ male mice, were administered DDT from gestational day 11.5 to postnatal day 5 to produce circulating levels of DDT in dams within the prenatal range associated with breast cancer in adult daughters. This perinatal DDT exposure significantly accelerated the development of palpable mammary tumors (hazard ratio = 3.7 (95% confidence interval 2.0-6.8; p<0.0001). We also aimed to study possible mechanisms for DDT increasing mammary cancer risk, including alterations in puberty tempo and the presence of breast cancer risk factors associated with impaired metabolism. We found that mice exposed to DDT perinatally had increased terminal end buds in their mammary glands late in puberty (postnatal day 63, p<0.05). Tumor-free mice exposed to DDT perinatally also had significantly elevated circulating glucose levels (p<0.05). The risk of mammary cancer associated with perinatal DDT exposure observed in mice closely mirrors that observed in women previously. Our findings raise the possibility that perinatal DDT exposure may increase risk of breast cancer through its effects on pubertal mammary gland development and/or on glucose homeostasis. Future research to further evaluate whether these effects are mechanisms by which perinatal DDT exposure accelerates breast tumorigenesis is highly warranted.

Citation Format: Tomoko Ishikawa, Jason Tong, Alexander Borowsky, Robert Cardiff, Michele La Merrill. Perinatal DDT exposure shortens latency of mouse mammary tumorigenesis [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A48.