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Dose-response analysis of the effects of Aroclor 1260 treatment on immune and endocrine endpoints in adult male rats Aloysius, Herve

Abstract

Polychlorinated biphenyls (PCBs) are prevalent environmental contaminants with a wide range of biological effects in wildlife, experimental animals, and humans. In order to quantify the toxicity associated with environmental PCB exposure, endocrine and immune endpoints were evaluated in a dose-response study using Aroclor 1260. Nine-week old male rats were treated with Aroclor 1260 in corn oil at dosages ranging from 0.025 to 156 mg/kg/day. Rats were treated by oral gavage for 10 consecutive days and killed two days after the last treatment. Eight days prior to sacrifice, rats received sheep red blood cells (2x10[superscript 8] SRBCs) by iv injection. Blood for determination of anti-SRBC IgM titer by enzyme-linked immunosorbent assay (ELISA) was collected 2 days prior to sacrifice, and at the time of death. Hepatic microsomes were prepared for subsequent cytochrome P450 (CYP) determinations. Only rats treated with the highest dosage of Aroclor 1260 exhibited decreased body weight gain. Aroclor 1260 had no effect on thymus, testis, ventral prostate or seminal vesicle weights, but liver weight was increased in rats treated at dosages greater than 0.13 mg/kg/day. Treatment with Aroclor 1260 decreased serum thyroxine (T4) levels in a dose-dependent manner, but serum luteinizing hormone (LH) and testosterone levels were unchanged. Aroclor 1260 also elicited dose-dependent suppression of humoral immunity as assessed by anti-SRBC IgM titer. In addition, total hepatic CYP content was increased at dosages greater than 1.25mg/kg/day. Immunoblot analysis indicated a dose-dependent induction of hepatic CYP2B enzymes up to a dosage of 15.6 mg/kg/day. Hepatic CYP1A protein content was also induced by Aroclor 1260 at dosages greater than 3.13mg/kg/day, but to a lesser degree than CYP2B. Determination of the various testosterone hydroxylase activities in hepatic microsomes revealed that hepatic CYP2B-, CYP3A-, and CYP2A1 -mediated activities were induced whereas CYP2C11 was suppressed. ED50 values of 0.66, 1.52, 3.99, 4.69, 5.38, 6.36 and 21.3 mg/kg/day were determined for total hepatic CYP induction, humoral immunity suppression, hepatic CYP2B2 induction, decrease in serum T4 levels, hepatic CYP2B1 induction, relative liver weight increase, and hepatic CYP1A2 induction, respectively. In summary, the results indicate that significant immunosuppressive, endocrine, and biochemical effects are produced in male rats by exposure to relatively low dosages (less than 6.25 mg/kg/day) of Aroclor 1260.

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