Barry M. Heatfield

Opposite effects of lead on chemical carcinogenesis in kidney and liver of rats.

The vast number of animal experiments designed to determine the tumorigenic effects of carcinogenic substances relate to a single compound and its effect upon one or more target tissues. Less commonly pursued are the interactions and results which may arise from the combination of two or more potential carcinogens in an experimental situation. One potentially important factor in the metabolism and ultimate fate of carcinogenic compounds in animal systems could be the degree of exposure of the animals to environmental pollutants, for example heavy metals. Recent evidence suggests that microsomal function may be inhibited or enhanced by specific heavy metal compounds.

Correlation of Cytokeratin Patterns with Histopathology during Neoplastic Progression in the Rat Urinary Bladder

The discrimination of atypical (premalignant) cells from invasive neoplastic cells in primary bladder lesions is a major diagnostic problem in cytopathology and surgical pathology. We have used an animal model of urinary bladder carcinogenesis to determine the specific changes which occur in the expression of certain cytokeratins (CK) during the progression of lesions from regenerative hyperplasia and carcinoma in situ to transitional cell carcinomas. At sequential time points following exposure of the rat bladder epithelium to N-methyl-N-nitrosourea in vivo, immunohistochemical staining of CKs was evaluated in ethanol-fixed samples from the induced urothelial lesions using commercially available anti-CK mouse monoclonal antibodies. Specific changes were found in the expression of CKs 13, 18, and 19 during the neoplastic progression of induced urothelial lesions in the rat. These changes included the reciprocal loss of expression of CK 19 and the reappearance of CK 18 as malignant tumors developed. Invasive cells also did not express CK 13. Our results, based on the rat model, are similar to those reported by others on CK expression in human bladder tumors. Because these changes in CK expression occurred at specific points in the progression of urothelial lesions, the antibodies utilized in this study may be helpful in predicting the invasive potential of cells present in cytopathological specimens and tissue biopsies from human urothelial lesions.

Chapter 8 Long-Term Explant Culture of Normal Human Prostate12

Publisher Summary This chapter summarizes recent findings of baseline studies on morphologic and histochemical alterations during long-term explant culture (24 weeks) of normal human prostate obtained at immediate autopsy of young adults. These findings demonstrate survival, mitosis, migration, and differentiation of prostatic basal cells in vitro . The only approach currently available to obtain abundant and viable normal prostate for in vitro studies is that based on the immediate autopsy. Viability is excellent, contamination of cultured tissues is infrequent, and long-term in vitro maintenance of epithelial cells is possible. As immediate autopsy can be performed on young adults, in whom benign prostatic hyperplasia (BPH) or latent adenocarcinoma is unlikely, normal prostate tissue can be obtained. One of the most striking changes, which take place in prostatic epithelium during early periods in vitro , is alteration in secretory cells. The principal histologic, histochemical, and fine structural changes in normal human prostate during long-term explant culture is summarized.