Toxic effects of acrylamide on the prostate of adult male albino rats and the role of pretreatment with vitamin C: immunohistochemical and DNA electrophoresis study

ABSTRACT

Acrylamide [AA] is a widely studied industrial chemical that is neurotoxic and mutagenic to somatic and germ cells. A considerable public concern about cancer risk from acrylamide-rich foods followed the announcement that high concentrations of acrylamide are found in starch-containing foods cooked at high temperatures. Data concerning the toxic effect and DNA damage of acrylamide in the prostate are still scarce, so the aim of this work tries to prove the toxic effect of acrylamide on the prostate by using histological and immunohistochemical studies, and to determine its potential mutagenic effect on DNA of the prostatic cells. The possible antimutagenic effect of ascorbic acid is also evaluated in this study. The experimental study was conducted on sixty adult male albino rats. Twenty adult control male albino rats [group I] subdivided into two subgroups, a and b, received distilled water and vitamin C orally. The experimental group [group II] is divided equally into four subgroups a, b, c, and d. Each group consists of ten rats, receiving acrylamide in a dose of 30 mg/Kg/day and 60 mg/Kg/day in subgroup II [a] and subgroup II [b] respectively. Subgroup II [c] and Subgroup II [d] received vitamin C in dose of 100 mg/kg /day one hour prior to acrylamide ingestion in a dose of 30 mg/Kg/day and 60 mg/Kg/day respectively for four weeks The histological picture of the prostate in experimental subgroup II a revealed signs of dysplasia in the form of nuclear pleomorphism, loss of nuclear polarity, enlarged nucleus with evident nucleolus and discontinuity of the basal cell layer. Some acini showed hyperplasia of its epithelial lining with apparent increase in stromal thickness. Rats in subgroup II b were presented with post atrophic hyperplasia in the form of atrophy and thinning of the epithelial lining of some acini. Focal areas of acinar hyperplasia with discontinuity of the basal cell layer were present. On pretreatment with vitamin C, the prostate showed apparent improvement of the epithelial cells height in subgroups II c and d. Immunohistochemical stained sections of acrylamide treated groups revealed estrogen receptor alpha [ER alpha] expressed as heavily brown dots in the prostatic stroma and in many nuclei of the acinar epithelial cells .The groups treated with vitamin C prior to acrylamide showed a slight decreased in ER alpha expression than groups treated with acrylamide alone. A significant increase in DNA damage was present in rats treated with 30 mg/kg/day acrylamide. Increasing the dose of acrylamide to 60 mg/kg/day led to significant increase in DNA damage of prostatic cells. Administration of vitamin C prior to acrylamide resulted in a significant decrease in DNA damage. It is concluded that acrylamide toxicity in adult male albino rat prostate [which was clarified by histological, immunohistochemical studies and DNA electrophoresis] had a direct dose response relationship and its association with acinar dysplasia serves as a warning that concurrent malignancy may exist. Vitamin C proved to have a protective role when received before exposure to acrylamide