Perinatal DDT Exposure Shortens The Latency Of Spontaneous Mammary Tumorigenesis In Mice
Michele LA MERRILL, University of California at Davis, United States
GONZALEZ E. 2
,
TRAN HOANG C. 3
,
ISHIKAWA T. 1
1 Environmental Toxicology, University of California, Davis, USA
2 Environmental Science & Management, University of California, Davis, USA
3 Animal Science, University of California, Davis, USA
Purpose. The contribution of exposure to dichlorodiphenyltrichloroethane (DDT) to breast cancer risk is controversial. The recent report by the International Agency for Research on Cancer (IARC) Monograph 113 Working Group concluded that “no clear association exists between breast cancer and DDT or DDE measured in samples of blood or adipose taken in adulthood; however, the possible importance of early-life exposure to DDT remains unresolved.”
Methods. We hypothesized that perinatal DDT exposure would result in shortened latency of spontaneous mammary tumorigenesis and increased incidence of lung metastasis. To test this hypothesis, C57BL/6J female mice, bred with B6.FVB-Tg(MMTV-PyVT)634Mul/LellJ male mice, were administered DDT from gestational day 11.5 to postnatal day 5 to achieve maternal serum levels within the upper range of the human cohort study that found a positive association between prenatal DDT exposure and breast cancer risk. We evaluated mammary lesion onset, growth and pulmonary metastasis in the transgenic heterozygotes. We also aimed to study possible mechanisms for DDT increasing mammary cancer risk including features of puberty development and the metabolic syndrome.
Results. Perinatal DDT exposure significantly shortened latency of spontaneous mammary tumorigenesis and was associated with a statistically insignificant doubling of the number of central pulmonary metastases per mouse. Prior to the development of mammary lesions, mice with perinatal DDT exposure had delayed pubertal maturation of mammary glands and elevated fasting blood glucose.
Conclusions. These studies in mice support the finding in humans that perinatal DDT exposure is associated with an increased risk of mammary tumors. Further, the data suggest that disrupted puberty and metabolism may contribute to the early incidence of mammary tumors in mice with perinatal DDT exposure. Our findings call for future research to further evaluate the effects and mechanisms of perinatal DDT exposure on breast tumorigenesis.
Funding source. National Institute Health ES023513, University of California