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Growth inhibition of a prostate tumor by alpha-difluoromethylornithine and by cyclophosphamide.

The effects of the ornithine decarboxylase suicide substrate, difluoromethylornithine (DFMO), and of cyclophosphamide, individually and in combination, on the growth of the R3327MAT-Lu prostate derived tumor were determined. DFMO decreased the growth rate and resulted in a 75% reduction in DNA content compared to the control group. Cyclophosphamide produced a greater inhibition of growth and resulted in a 96% reduction in DNA content relative to the control. DFMO in combination with cyclophosphamide provided no greater inhibition of tumor growth than that of cyclophosphamide as a single agent. Further, in the schedule used in this experimental protocol the toxicity to the host of the drug combination was additive.

Animals↗

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Prostatitis.

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Acute Disease↗

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Tobacco smoking, occupation, and p53 nuclear overexpression in early stage bladder cancer.

Epidemiological studies show an increased risk of bladder cancer associated with tobacco smoking and occupational exposures. Certain carcinogens in tobacco and occupational exposures cause DNA damage and may produce specific mutations. TP53 is considered a common target for carcinogenic agents, and mutations of this gene are reported to be the most frequent nuclear abnormalities in human cancer. In order to investigate the relationship between tobacco smoking, occupations, and altered patterns of p53 expression, we have analyzed a group of 109 incident patients with superficial transitional cell carcinoma of the bladder. We assessed p53 nuclear overexpression by the use of anti-p53 antibody PAb1801 and immunohistochemistry, and identified 45 of 109 patients (41%) displaying p53-positive phenotype. We observed a significant association between the number of cigarettes smoked per day and p53 nuclear overexpression (p = 0.02). The odds ratios were 2.3 for those smoking 1-2 packs per day and 8.4 for smoking more than 2 packs per day. Similar estimates were obtained after controlling for age, sex, and race. Elevated odds ratios were also observed for dye-/ink-related (odds ratio = 2.0; 95% CI, 0.4-9.4) and cooking-related occupations (1.8, 0.6-5.0), although those were not statistically significant. These data support the hypothesis that certain carcinogens derived from cigarette smoking and occupations may induce TP53 mutations, which in turn are involved in early steps of bladder carcinogenesis.

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