Estrogenic activity of zinc pyrithione: an in vivo and in vitro study

Zinc pyrithione (ZP) is commonly used to prevent dandruff and seborrheic dermatitis. Many consumers are exposed daily to high doses of ZP, causing serious concerns about its toxicity. The reproductive and developmental toxicities were previously reported in pregnant rats. However, the estrogenic activity of ZP at varying degrees of exposure has been rarely studied. Thus, we performed an uterotrophic assay, E-screen assay, and gene expression profiling to assess the estrogenic activity of ZP. For the uterotrophic assay, ZP (2, 10, or 50 mg/kg/d) was subcutaneously administered to ovariectomized rats every day for three days. Uteri were extracted 24 hours after the last dose. Then, wet and blotted uterine weights were measured. For the E-screen essay, MCF-7 cells (a breast cancer cell line) were exposed to 10⁻⁹ to 10⁻⁶ M of ZP, and cell proliferation was then measured. For the gene expression analysis, changes of gene expression levels in uterine samples taken for the uterotrophic assay were analyzed. In the uterotrophic assay, the concentration of ZP had no significant effect on uterine weight. In the E-screen assay, ZP at any concentration showed no significant increase in MCF-7 cell proliferation, compared to the control group. However, 10⁻⁶ M of ZP significantly reduced cell viability. The changes in gene expression slightly differed between the ZP and control groups. The in vivo and in vitro assays, together with gene expression analysis, demonstrated that ZP showed no significant estrogenic activity.

Estrogenic activity of zinc pyrithione: an in vivo and in vitro study

Zinc pyrithione (ZP) is commonly used to prevent dandruff and seborrheic dermatitis. Many consumers are exposed daily to high doses of ZP, causing serious concerns about its toxicity. The reproductive and developmental toxicities were previously reported in pregnant rats. However, the estrogenic activity of ZP at varying degrees of exposure has been rarely studied. Thus, we performed an uterotrophic assay, E-screen assay, and gene expression profiling to assess the estrogenic activity of ZP. For the uterotrophic assay, ZP (2, 10, or 50 mg/kg/d) was subcutaneously administered to ovariectomized rats every day for three days. Uteri were extracted 24 hours after the last dose. Then, wet and blotted uterine weights were measured. For the E-screen essay, MCF-7 cells (a breast cancer cell line) were exposed to 10⁻⁹ to 10⁻⁶ M of ZP, and cell proliferation was then measured. For the gene expression analysis, changes of gene expression levels in uterine samples taken for the uterotrophic assay were analyzed. In the uterotrophic assay, the concentration of ZP had no significant effect on uterine weight. In the E-screen assay, ZP at any concentration showed no significant increase in MCF-7 cell proliferation, compared to the control group. However, 10⁻⁶ M of ZP significantly reduced cell viability. The changes in gene expression slightly differed between the ZP and control groups. The in vivo and in vitro assays, together with gene expression analysis, demonstrated that ZP showed no significant estrogenic activity.

Biodistribution of Adenovirus p53 Following Intraperitoneal Administration in Mice

Reproductive toxicology is relatively new to the field of gene therapy, and is a very important issue for the safety. An important safety concern of gene therapy products is the distribution of vector beyond target organs. This is particularly important if vector distributes to gonads, raising the possibility of inadvertent germ-line transmission. In addition, for indications such as prostate cancer and ovarian cancer, the proximity of the point of viral administration to organs of the reproductive system raises concerns regarding inadvertent germ-line transmission of genes carried by the virus. To evaluate the reproductive toxicity of in vivo E1-deleted replication-incompetent adenoviral vector encoding p53 or lacZ, we studied the biodistribution and potential germ-line transmission of the vector. Both male and female Balb/c mice were injected with 1x10(8) pfu of Ad-CMV-LacZ or Ad-CMV-p53. DNA and RNA extracted from major organs including gonadal tissues were analyzed for vector sequences and expression. The PCR analysis showed that there were detectable vector sequences in liver, kidney, spleen, seminal vesicle, epididymis, prostate, ovary, and uterus. The RT-PCR analysis showed that Ad-CMV-LacZ or Ad-CMV-p53 viral RNA were present in spleen, prostate and ovary. Vectoradministered female and male mice were mated and their offspring were evaluated for germ-line transmission of the adenoviral vector. The PCR analysis showed no evidence of germ-line transmission, although vector sequences were detected in DNA extracted from gonadal tissues. Together, we conclude that the risk of the inadvertent germ-line transmission of vector sequences following intraperitoneal injection of adenovirus is extremely low, although vector distributed to gonadal tissues.