No abstract

Epidemiologic data reveal that the incidence rate of prostate gland carcinoma among the black population in the United States (US) is several times higher than among Nigerians. A collaborative study between the two countries was undertaken, and blood hormone (testosterone [T], dihydrotestosterone [DHT], estrone [E1], estradiol [E2], and prolactin [P1]), total acid phosphatase (TP), and prostatic acid phosphatase (PAP) profiles in the two population groups were compared. In the US groups (patients and controls) there were significantly higher levels of T (P less than 0.01) and E1 (P less than 0.05) compared with the Nigerians. Also, the US patients had significantly higher levels of T (P less than 0.05) and E1 (P less than 0.01) compared with their matched controls. In the Nigerians T but not E1 levels were significantly lower (P less than 0.05) in patients compared with controls. DHT, E2, and P1 were not significantly different in patients and controls between and within the populations. Nigerian patients had higher levels (P less than 0.001) of TP and PAP compared with US patients. It is concluded that differences in blood hormone profiles in the two population groups are based on factors other than the genetic makeup of the populations.

A comparison of carcinoma of the prostate gland in a low-incidence Nigerian (Ibadan) population and a high-incidence U.S. Afro-American (Washington, D.C.) population was the purpose for this study, initiated in 1973. The frequency of carcinoma (micro- and invasive) was determined in consecutive necropsy cases from hospitals in Ibadan, Nigeria, Accra, Ghana and Washington, D.C. The results of these clinical, epidemiologic and morphologic studies are reported. Clinically, the peak incidence of carcinoma of the prostate in Nigerian males in Ibadan and in American males in Washington, D.C. was in the 65-74 age group. The median age of patients was 66.4 years in Ibadan and 69.2 years in Washington, D.C. Seventy-five percent of Nigerian and 49% of American patients were in stages III and IV. Overall, the distribution by grade of neoplasms in surgical material from Ibadan and Washington, D.C. was similar. Plasma testosterone and estrone levels were significantly higher (p < 0.05 and p < 0.001) in U.S. patients than in U.S. controls and higher (p < 0.001 and p < 0.05) in U.S. patients than in Nigerian patients with prostatic carcinoma. Plasma testosterone levels were significantly lower (p < 0.05) in Nigerian patients than in Nigerian controls. Estrone levels were not significantly different in Nigerian patients than controls. Nigerian patients were more sexually active throughout their lives than American patients; however, they reported a higher incidence of impotence than U.S. patients in the immediate 5 years preceding the diagnosis of prostatic carcinoma. Nigerian respondents (patients and controls) arrived at puberty later than their American counterparts. Within each of the two population groups, the factor with the highest relative risk ratio was lower urinary tract symtoms occurring 10 years or longer before the onset of the present complaints which led to the diagnosis of prostatic carcinoma. Nigerian and U.S. patients were more sexually active than controls. Microcarcinoma (incidental, latent) of the prostate gland occurred with a frequency of 11.8% and at an age-adjusted incidence rate (world standard) of 40.6 per 1000 necropsies in the sampled U.S. black male population. The age-adjusted incidence rate (world standard) for microcarcinoma in the combined West African (Accra and Ibadan) series (36.7/1000) was almost equal to the rate (40.6/1000) in the Washington, D.C. series.

Transforming growth factor-beta-1 (TGF-beta 1) null mutant mice have no gross developmental abnormalities at birth but succumb to multifocal inflammatory lesions that lead to organ failure and death about 20 days after birth. Treatment with anti-inflammatory and immune suppressive agents, such as rapamycin, reduces the severity and extent of inflammatory infiltrates in the liver and can prolong the life of knockout (KO) mice compared to untreated null mice. To determine whether there is an associated hepatic phenotype, livers of "young" (< 3 weeks), "old" (> 3 weeks), and age-matched wild-type (WT) mice were studied using light and electronmicroscopy. On light microscopy, old KO mice had foci of mononuclear cells in liver parenchyma in addition to scattered foci of megalocytosis. Intracytoplasmic vacuoles, some of which were juxtanuclear in location, were also seen but these were most prominent in the oldest (10 weeks) rapamycin-treated mouse. In the untreated young KO mice, there were only foci of mononuclear cells in the liver parenchyma and portal tracts and variable numbers of binucleated hepatocytes. Ultrastructurally, there was a significant increase in the number of mitochondria in livers of the old KO mice, when compared either to the age-matched wild-type or to the young KO mice (p > .001). Hepatocytes from all KO mice showed increased numbers of hypertrophied or enlarged Golgi complexes compared to age-matched wild-type mice. Intracytoplasmic canaliculi lined with microvilli were seen in livers of old KO mice, but were absent in the young KO and wild-type mice. Primary cultures of hepatocytes, derived from livers of both young and old KO mice, showed similar changes on phase contrast and electronmicroscopy. These included juxtanuclear vacuoles, intracytoplasmic canaliculi, enlarged Golgi vesicles, and increased numbers of autolysosomes. Phenotypic abnormalities of mitochondria were either minimal or absent in cultured KO hepatocytes. The findings demonstrate, for the first time, that targeted disruption of the TGF-beta 1 gene in mice results in an altered ultrastructural phenotype of hepatocytes. The data suggest that TGF-beta 1 may be required for normal development and regulation of subcellular organelles in hepatocytes and may be essential for physiological functions involving mitochondria and Golgi complex.

MarylandThe carcinogenic effects of crystalline silica in rat lungs were extensively demonstrated by many experimental long-term studies, showing a marked predominance for adenocarcinomas originating from alveolar type 11 cells and associated with areas of pulmonary fibrosis (silicosis). In contrast with its effects in rats, silica did not induce alveolar type 11 hyperplasia and lung tumors in mice and hamsters, pointing to a critical role for host factors. Using these animal models, we are investigating the role of cytokines and other cellular mediators on the proliferation of alveolar type 11 cells. Immunohistochemical localization of TGF-,B1 precursor in alveolar type 11 cells adjacent to silicotic granulomas was shown to occur in rats, but not in mice, and hamsters, suggesting a pathogenetic role for this regulatory growth factor. Recent investigations in our laboratory on the biologic mechanisms of crystalline silica included determination of anionic sites on crystalline silica surfaces by binding of the cationic dye Janus Green B; binding of crystalline silica to DNA, demonstrated by infrared spectrometry; production of oxygen radicals by crystalline silica in aqueous media; induction of DNA strand breakage and base oxidation in vitro and its potentiation by superoxide dismutase and by hydrogen peroxide; and induction by crystalline silica of neoplastic transformation and chromosomal damage in cells in culture. On the basis of these in vitro studies, we propose that DNA binding to crystalline silica surfaces may be important in silica carcinogenesis by anchoring DNA close to sites of oxygen radical production on the silica surface, so that the oxygen radicals are produced within a few A from their target DNA nucleotides. -Environ Health Perspect 102(Suppl 10): 159-164(1994)