Investigation of silicone oil and fumed silica in an adjuvant animal model.

Human adjuvant disease is the label given to a syndrome that resembles a connective tissue disease such as scleroderma and that has been hypothesized to follow augmentation mammoplasty with silicone gel implants or silicone with adulerants. To date, there is no proof that pure silicone is the cause of these symptoms. The cases presented in the literature suggest a comparison to the events seen in the rat adjuvant arthritis model. Male Lew/SsN rats (n = 65) were used. To evaluate both the adjuvant and antigenic properties of the gel implant, variations of the standard Freund's complete adjuvant inoculum were prepared. Tested were the abilities of low molecular weight silicone to act as an adjuvant and for fumed silica to act as an antigen by modifying a rat adjuvant arthritis model to include silicone and fumed silica. On day 0, 0.25 ml of each inoculum was injected intradermally into the plantar aspect of the hindfoot of each rat. The foot diameter was recorded at each time period, compared with the contralateral hindfoot, and normalized to controls at regular time periods over the course of 120 days. Silicone oil did not act as an adjuvant. Furthermore, fumed silica alone did not act as an antigen; however, it is capable of eliciting a reaction that is both delayed and uncharacteristic of the rat adjuvant arthritis model. These results indicate that "human adjuvant disease" may be inappropriate and misleading.

Suppression of male-specific cytochrome P450 2c and its mRNA by 3,4,5,3',4',5'-hexachlorobiphenyl in rat liver is not causally related to changes in serum testosterone.

Rat cytochrome P450 2c (P450 gene IIC11) is a constitutive, male-specific hepatic enzyme which is suppressed greater than 90% by treatment with 3,4,5,3',4',5'-hexachlorobiphenyl (HCB) [H. N. Yeowell et al. (1987) Mol. Pharmacol. 32, 340-347]. HCB also decreases serum testosterone levels in adult male rats (greater than 98% loss). The present study assesses whether the suppression of P450 2c by HCB is a direct result of its effects on serum testosterone levels. Further, the site along the hypothalamic-pituitary-testicular axis at which HCB acts to depress testosterone secretion was examined. Administration of the synthetic androgen methyltrienolone to HCB-treated rats failed to prevent the suppression of P450 2c mRNA and its associated microsomal steroid 16 alpha-hydroxylase activity under conditions where it effectively reversed the large decrease in P450 2c mRNA and steroid 16 alpha-hydroxylase activity produced by castration. Hepatic steroid 6 beta-hydroxylase activity, which is catalyzed primarily by P450 2a (P450 gene IIIA2), was also suppressed by HCB and was not protected by methyltrienolone. Administration of either human chorionic gonadotropin, an analog of pituitary-derived luteinizing hormone, or the hypothalamic luteinizing hormone releasing hormone elevated serum testosterone levels to a much smaller extent in HCB-treated rats than in control rats. These results indicate that the effects of HCB on serum testosterone levels reflect its effects on testicular function rather than the pituitary or hypothalamus. However, the present study demonstrates that the consequential reduction in serum testosterone levels in HCB-treated rats is not causally related to the reduction in hepatic P450 2c levels. Thus, HCB must also act on some other regulatory mechanism involved in the expression of this protein.