Abstract 1580: Age-related difference in the susceptibility phthalate-induced injury in Sprague-Dawley rat

Abstract Di-2-ethylhexyl phthalate (DEHP), a commonly used plasticizer of synthetic polymers causes liver tumorigenesis, and both short and long-term effects on the reproductive system of male rats. Whether initial exposures to DEHP in early developmental stage affect the susceptibility to injury by subsequent exposures later in life remain unknown. Pregnant dams of Sprague Dawley rats were gavage with vehicle, 100 or 750 mg/kg bw/day of DEHP from Gestational Day 14 (GND14) until birth. After resting for twenty days, at postnatal day 21 (PND21) male offspring were gavage with vehicle, DEHP (100 or 750 mg/Kg/d) for 14 days (PND21-35). On PND35, offspring were sacrificed, serum testosterone (T) levels, body and organ (testis, liver and kidney) weight were examined. The data reveals that DEHP 750 mg/Kg/d but not 100mg/Kg/d treatment were sufficient to cause damage to testis when exposures occurs during either gestational or peripubertal (PND21-35) period. Interestingly, our data also indicated that subsequent exposures to DEHP (100 mg/Kg/day) in utero and at peri-pubertal stage were also effective to causing significant injury to testis. The serum T levels were reduced in all DEHP treatment groups. Next, we investigated the effects of peripubertal exposure to DEHP on the susceptibility to injury by subsequent exposure during adulthood. PND21 rats were subjected to oral administration of Oil, DEHP (100mg/kg/day or 750mg/kg/day) for 14 days (PND21-35). The rats were allowed to rest for 25 days until PND60. At PND60, rats were divided into groups and subsequently exposed to oil or DEHP (100 or 750 mg/Kg/d) for 14days (PND60-74). At PND74 the rats were sacrificed, serum T levels, body and organ weights were determined. Interestingly, no significant injury was observed in any of the treatment groups. Instead, and enhanced serum T levels were observed in DEHP-treated adult rats compared to control. Together, this study shows that the susceptibility to injuries following subsequent DEHP exposure is age-dependent, with immature male rats more susceptible while adults are resistant. In addition, the data also indicated that injuries sustained during peri-pubertal exposure are at least in part reversible. This work was supported by NIH-NIGMS-SCORE 2 grant SC2GM099578. Citation Format: Kassim Traore. Age-related difference in the susceptibility phthalate-induced injury in Sprague-Dawley rat. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1580. doi:10.1158/1538-7445.AM2014-1580