M. Lans

variations in serum alkaline dnase activity. A new means for therapeutic monitoring of malignant lymphomas

Our previously published clinical results suggest that the variations in serum alkaline DNase activity (SADA) could be a reliable marker for the therapeutic monitoring of different human malignancies. The aim of the study documented in this was to determine SADA variations in 27 patients suffering from malignant lymphomas (Hodgkins and non‐Hodgkins). Patients continued to be observed after therapy. The blood samples were collected before treatment (Time 0), during several days from the onset of each treatment (Phase I), and weeks after the last therapy (Phase II). A decrease in the serum alkaline DNase activity during the first treatment indicates a good clinical response; no decrease indicates a nonresponse to treatment (Phase I). The Phase II data can be used to predict the long‐term evolution of the disease. In patients who respond to therapy three types of variations of SADA are observed during this phase. A progressive regain of SADA up to a value exceeding the level of initial value (T0) correlates with a complete remission. An incomplete regain of activity corresponds to a partial remission. No regain of SADA precedes death.

Serum alkaline DNase activity in normal or nonhospitalised individuals

According to previous observations, the variations in serum alkaline DNase activity (SADA) appeared to be useful in monitoring malignant disease. In this study, SADA was measured in 625 individuals to explore nontumor-related factors which may influence SADA levels. The overall range in SADA was 0.2-82.3 kU/l. Women aged 50-79 years had higher (p less than 0.001) levels of SADA than younger females. A similar but less consistent effect of age was noticed in men (0.01 less than p less than 0.05). Older men had lower (0.01 less than p less than 0.05) SADA levels than the older women. Old women substituted with estrogens had lower (0.01 less than p less than 0.05) levels of SADA than those not treated with estrogens. SADA levels in pregnancy as well as postparturition were lower (p less than 0.001) than SADA values in nonpregnant females of similar age. In fertile women, no SADA variation was observed during the menstrual cycle and there was no significant effect of contraceptive pills. In males, SADA seemed unrelated to testosterone or cortisol levels but varied during the day. Smoking, alcohol consumption and drug therapy appeared to be without effect on SADA.

Characteristic variations of serum alkaline DNase activity in relation to response to therapy and tumor prognosis in human lung cancer

The objective of the present study was to evaluate serum alkaline DNase activity (SADA) variations as a useful means of lung cancer monitoring therapy. SADA was measured in 40 patients with non-small cell and small cell carcinomas. Blood samples were collected before (Time 0), during the treatment and months after therapy. A decrease in SADA during the first treatment indicates a good clinical response, whereas an absence of decrease indicates a non-response to treatment. In patients who respond to therapy, three types of variations of SADA are observed during the clinical course. A progressive regaining of SADA up to a value largely exceeding the level of the initial SADA value (T0) correlates with a complete remission. An incomplete regaining of enzyme activity corresponds to a partial remission, whereas no regaining of SADA precedes a fatal evolution. Such variations in SADA observed in the 40 patients with lung carcinomas support our previously published clinical results, confirming that the variations of SADA could be a reliable marker for the therapeutic monitoring of different human malignancies.

Predictive value of serum alkaline DNase activity variations in treatment of head and neck cancer.

The aim of this study was to evaluate the variation in serum alkaline DNase activity (SADA) as a means of therapeutic monitoring in patients with head and neck cancer. Blood samples from 40 patients were collected before, during, and some weeks up to months after therapy. A decrease in SADA during treatment was usually associated with a primary clinical response, while no decrease indicated non-response to therapy. In patients with complete tumor regression the initial decrease of SADA was usually followed by an increase exceeding the initial level. A similar increase was not observed in patients with tumor progression.

Comparison of different models of rat liver carcinogenesis: conclusions from a systemic analysis.

Different protocols of chemically induced hepatocarcinogenesis were applied to Wislar rats under identical experimental conditions. The following conclusions may be drawn after an analytic comparison of these results. Various chemical carcinogens show different carcinogenic capacities. Diethylnitrosamine is more potent than N-nitrosomorpholine which is more active than 2-acetylaminofluorene. A short-term exposure to such carcinogens is sufficient to initiate but not necessarily to complete the carcinogenic process. It can be promoted to completion by either a noncarcinogenic promoter or a carcinogen. From a systemic point of view, it appears that, as in the skin models, two-step protocols are not always equivalent to protocols using the same agent during the whole treatment. Moreover, the results observed with a multistep protocol indicate that during the initiating phase the carcinogen plays a selective role distinct both from a pure initiating role and from the promoting effect. The results obtained lead to the conclusion that the distinction between initiation and promotion remains purely operational as it still does not correspond to the nature of well-established biologic processes.

Separate isolation of cells from nodules and surrounding parenchyma of the same precancerous rat liver: biochemical and cytochemical characterization.

Various enzyme and metabolic alterations have been observed in the hyperplastic nodules which appear during the hepatocarcinogenesis. These alterations have been mainly specified by histochemical observations. In this report, a technique of hepatocyte isolation is described which enables the separation of 2 cellular fractions, respectively, from the nodules and from the surrounding parenchyma of the same liver of a rat previously treated with a hepatocarcinogen. Such a technique allowed parallel analysis of both cellular populations by biochemical and cytochemical techniques.

Nucleolar changes during the first steps of experimental hepatocarcinogenesis in rats

Silver stainability of hepatocytes as an expression of nucleolar activity was studied in vivo during rat hepatocarcinogenesis. Male Wistar rats were injected with one dose of diethylnitrosamine (200 mg/kg body weight dissolved in 0.9% NaCl), followed by a selection procedure with a short exposure to 2-acetylaminofluorene in combination with a proliferative stimulus, such as the administration of CCl4. Finally, after 1 week of a normal diet, some of the rats were treated with phenobarbital. After enzymatic isolation, the hepatocytes were silver stained; the estimation of nucleolar activity was determined by a cytomorphologic analysis of the silver-stained nuclei. It was demonstrated that during the first steps of hepatocarcinogenesis, both diethylnitrosamine, as initiator, and phenobarbital, as promotor, induce modifications of the nucleolar morphology in silver-stained hepatocytes.

Mutagenicity, Carcinogenicity, and Teratogenicity of Halogenated Hydrocarbon Solvents

Seven chlorinated solvents (methylene chloride, chloroform, carbon tetrachloride, trichloroethylene, 1,1,1-trichloroethane, 1,2-dichloroethane, and tetrachloroethane) widely used in industry for metal degreasing, in extraction processes, as refrigerants or aerosol propellants, paint removers, and starting material for the manufacture of fluorocarbons have been reviewed.