Ulla Iversen

Cell kinetics in Burkitt lymphoma.

Abstract The cell kinetics of small pieces of diagnostic biopsies of African cases of Burkitt tumour was studied in 13 cases of primary tumour, 4 cases of recurring tumour and three cases of non-Burkitt lymphosarcomas in short time tissue culture with tritiated thymidine, ( 3 HTdr) in the medium. The in vivo uptake of 3 HTdr was also studied in two patients in Stage IV. The uptake of 3 HTdr by tumour cells in ascites fluid was studied in one patient. In 7 patients Colcemid was given 2–4 hr prior to a biopsy, and the number of Colcemid-arrested mitoses counted. In 4 cutaneous nodules of Burkitt tumour, the actual growth rate was measured. The results were analysed by means of a mathematical tumour growth model (see Appendix by R. Bjerknes). The kinetic parameters observed were as follows: actual clinical doubling time 66 hr, labelling index 17·34% , rate of cells entering DNA-synthesis 2·71% per hr, mitotic index 1·27% , rate of cells entering mitosis 1·75% per hr, duration of G 1 16·5 hr, duration of DNA-synthesis 6·5 hr, duration of G 2 2 hr, duration of mitosis 0·7 hr, potential doubling time based on labelling indices 25·6 hr, potential doubling time based on number of Colcemid arrested mitosis 39·6 hr, cell loss in the G 2 phase 30% , total cell loss factor 69% of maximum possible cell gain.

Cell kinetics of African cases of Burkitt Lymphoma: A preliminary report☆

Abstract Small pieces of fresh biopsies of tumour tissue from 17 patients with African Burkitt lymphoma and three patients with other non-Burkitt undifferentiated lymphosarcomas were transferred to tissue culture medium with tritiated thymidine and Colcemid. Specimens were fixed after 1, 2, 3 and 4 hr respectively, autoradiographed, and labelling indices determined. In two patients in stage IV, tritiated thymidine was given intravenously every 6 hr for 2 days. Biopsies were obtained 1 hr after the first injection, and then on the first and the second day, and the labelling indices were determined. In the same two patients the diameters of cutaneous tumour nodules were also measured for 3 days. The results show that in the Burkitt tumours analyzed, the mean cell “birth-rate” was 2·71% of all cells per hr, which gives a potential doubling time of 25·5 hr. The actual doubling time was 66 hr. The growth fraction was estimated to be 90–100% of all cells. The rate of cell loss was calculated to be about 70% of the rate of cell renewal. The rate of cellular proliferation in the three lymphomas of non-Burkitt type was 3·78% of all cells per hr, which gives a potential doubling time of 18·3 hr. The rapid rate of cell turn-over in the Burkitt tumour may kinetically explain the rapid response to cytostatic treatment, but it can not explain why Burkitt tumours seem to be more curable than other lymphomas. Immunological mechanisms may be responsible for this.

Two cases of benign vaginal rhabdomyoma

Two cases of benign vaginal rhabdomyoma, which occurred in women aged 38 and 54 years, are reported. The macroscopic and microscopic appearance is described. The literature on this rare tumour is reviewed and the differential diagnoses are discussed. Local excision is considered adequate treatment.

Some effects of bleomycin on the proliferation, maturation time and protein synthesis of hairless mouse epidermis.

Hairless mice were given 2 mg Bleomycin i.p. in 1‐0 ml saline on two successive days. By a stathmokinetic method, by micro‐flow fluorometry and by autoradiography certain kinetic parameters were measured during 10 days after the last injection. Cell counts were made and the turnover time of the differentiating cells estimated. Protein synthesis was estimated by the uptake of radioactive histidine, and dry cell mass measured by weighing. Bleomycin affected cell proliferation in the epidermis by depressing biphasically both the number of cells in, and the passage of cells through, the cell cycle phases: S, G2 and M, most probably by directly affecting late Gj cells and cells in mitosis. The time between the two minima of depressed DNA synthesis corresponded to the mean generation time of the basal cells. Histidine uptake and dry cell mass were slightly affected, but the turnover time of the differentiating cells was prolonged.

The carcinogenic effect of TPA (12-0-tetradecanoylphorbol-13-acetate) when applied to the skin of hairless mice

SummaryGroups of hairless mice received one, two, five and fifty applications of 20 nmoles TPA (12-0-tetradecanoylphorbol-13-acetate) on the skin of the back, and were observed for 20 months. The animals developed some papillomas, some squamous cell carcinomas, some fibrosarcomas of the dermis, and some malignant and benign tumours in internal organs. There was a small, not significantly different, incidence of benign and malignant tumours after 1, 2 and 5 paintings, and a significantly higher tumour incidence after 50 applications. Apart from reticuloses, which are commonly seen in these animals, the occurrence of other tumours is believed to be related to the TPA treatment. The results are interpreted as shrowing that TPA, like croton oil, should be regarded as a complete carcinogen.

Tumours of the skin.

Cancer of the skin in Ugandan Africans is found almost exclusively in association with some previous damage. The most frequent predisposing lesion is a tropical phagedenic ulcer usually located on the lower leg. Tumours also occurred following burns or bites. Tumours were found more commonly among people from the west of the country. The cause of this regional variation is unknown. Tumours were predominantly well differentiated squamous carcinomas. Basal-cell tumours were only rarely seen. Tumours induced by solar damage were seen in albinos and on the conjunctiva but rarely on normally pigmented skin.

Effects of bleomycin on the epidermal content of growth-regulatory substances (chalones).

Hairless male mice were given 2 mg Bleomycin i.p. on two successive days. At different time intervals from 1 to 10 days after the last Bleomycin injection, groups of animals were killed and water extracts of homogenized skin were made.