Nor-nitrogen mustard is an alkylating agent used in kilogram quantities in the production of various cytostatics. It has been shown to be mutagenic in vitro, and therefore must be regarded as a health hazard. We have studied the environment and blood of a small group of individuals working with nor-nitrogen mustard. New chemical methods for measuring surface contamination were used to make comparisons with ambient air levels of nor-nitrogen mustard. Surprisingly high levels of surface contamination were found even after decontamination, which has led to new decontamination routines and the establishment of wipe test limits of 0.5 microgram nor-nitrogen mustard/dm2. The wipe test has proved effective in following the day-to-day routine handling of nor-nitrogen mustard. Blood samples were taken before, during, and after production runs and analyzed for the frequency of chromosome aberrations (CAs), sister chromatid exchanges (SCEs), and somatic (HPRT) mutations. No significant differences in chromosome aberrations, SCEs, or somatic mutations were found in the peripheral blood from production workers before, during, or after handling of nor-nitrogen mustard. Nor was any difference found between the production workers and a local control group. However, the local controls' chromosome and HPRT frequencies appeared to be somewhat high, demonstrating the problems involved in these types of studies, in which the group sizes are small.

Adsorption↗

PubMedDate not supplied

Fine needle biopsy as a method for following ploidy changes in the Dunning R-3327 rat prostate tumour.

The use of fine needle biopsies for the collection of cells for flow cytometry was investigated using the Altman Dunning R-3327 rat prostate tumour. Five rats were castrated 150 days after tumour implantation. Multiple fine needle biopsies were performed 138, 194 and 220 days post implantation and the results compared to those from intact animals. A small aneuploid peak was found at the 2.8c position in intact animals. Although tumour growth was slowing down in castrates, indicating hormone independency but sensitivity, no change in flow cytometric profile could be demonstrated. This indicates that, in this model, no correlation between aneuploidy and hormone independence exists. The fine needle biopsy method proved to be easy and reliable for tumours of above 1 cm3 in volume.

Animals↗

PubMedDate not supplied

Uptake and metabolism of estramustine in the Dunning R3327H tumour.

A time-dependent plasma, tumour cell and nuclear uptake was found after intraperitoneal 3H-estramustine administration, in rats bearing the Dunning H tumour. Uptake of the drug into tumour cells had not reached a maximum after 4 h, whereas no real change was seen in the nuclear fraction after 2 h. Binding to the nuclear protein matrix of Dunning H tumour cells of 3H-estramustine was also found (2.46 pmol/g protein). High performance liquid chromatography demonstrated the existence of estramustine, its oxidized metabolite estromustine, estradiol and estrone in the plasma and the tumour after intravenous administration of 100 microCi 3H-estramustine.

Animals↗

PubMedDate not supplied

C-banding of two Walker 256 rat carcinoma cell lines sensitive and resistant to bifunctional mustards.

Walker 256 rat carcinosarcoma cell lines sensitive (WS) or resistant (WR) to bifunctional nitrogen mustards have modal chromosome numbers of 60 and 55 respectively. Karyotype analysis revealed that these cell lines have retained the major marker chromosomes present in the original in vivo Walker tumours. One new marker chromosome, a metacentric, was found in the WR cell line. C-banding revealed that in the WS cell line the secondary constriction of the marker chromosome was stained, whereas no staining was found on this chromosome in the WR cell line. Three autosomes containing very prominent non-centromeric C-bands were present in WS but not in the WR cell line which has 2 other chromosomes with minor C-bands. As non-centromeric C-bands do not occur in the normal rat karyotype, these are easily identifiable specific tumour markers for these two cell lines.

Alkylating Agents↗

PubMedDate not supplied

Inhibition of angiogenesis and metastases of the Lewis-lung cell carcinoma by the quinoline-3-carboxamide, Linomide.

Linomide has antitumor effects when administered in vivo but not in vitro. Recent data indicate that at least part of this effect can be attributed to anti-angiogenic properties. The aim of the present investigation was to study the anti-angiogenic effects of Linomide on early tumor-induced angiogenesis in vivo, using a newly developed skinfold chamber technique in the mouse, and to relate this to the effect of Linomide on the number of metastases that develop from a s.c. implanted tumor. Tumor spheroids of Lewis lung cell carcinoma (LLC) with a diameter of about 800 microns were implanted in dorsal skinfold chambers inserted on CB6/Fl mice. Tumor cells were pre-labelled with a fluorescent vital dye (CMTMR), which allowed the estimation of the growth of the implanted tumor spheroids. Linomide, given orally from day 7 to day 11, reduced the incidence of lung metastasis arising from LLC tumors at day 21 in a dose-dependent manner, a 55% reduction being found at a dose of 50 mg/kg/day (N = l9 for the controls and N = 10 for treatment groups). In the dorsal skinfold chamber, the vascular network in Linomide treated animals (100 mg/kg/day, N = 22) was more heterogenous, large areas within the tumor being completely avascular; in addition, capillary density at the tumor site was reduced by 34% 6 days after implantation and by 39% after 14 days. In the control group (N = 16), tumor volume doubling time was not significantly different in the early avascular part of the observation period as compared to the later vascular phase; this indicates that the growth of these micro-tumors in the early avascular phase is not angiogenesis dependent. However, in the Linomide treated animals, tumor volume doubling time was significantly prolonged by 42% during the later part of the observation period. Taken together, the data indicate that the prolongation of the tumor doubling time is due to the anti-angiogenic activity of Linomide.

Animals↗