Brigitte Hesse

Two-stage skin carcinogenesis by systemic initiation of pregnant mice with 7,12-dimethylbenz(a)anthracene during gestation days 6–20 and postnatal promotion of the F1-generation with the phorbol ester 12-tetradecanoylphorbol-13-acetate

SummaryThe DMBA-TPA-mediated two-stage skin carcinogenesis experiment was modified in that pregnant mice were systemically treated once during pregnancy with the carcinogen. Intragastric application times were fetal days 6, 8, and 10–20. A control group of pregnant mice received repeated doses (from days 8–20) of sesame oil, which was used as a solvent for DMBA.At the age of 12 weeks, the offspring of the control group were divided into two groups, one of which was left completely untreated, the other received TPA applications over 26 weeks.The 12-week old F 1-progeny of each transplacentally initiated group was also divided into subgroups, which either received no further treatment (subgroups A) or were promoted with TPA (subgroups B). Neither the F 1-animals of the two control groups nor that of the transplacentally initiated but postnatally not promoted subgroups 6A–20A developed skin tumors. The same holds true for the TPA-promoted offsprings of mother animals which had received DMBA at days 6 and 8 of gestation.Skin tumor development after TPA promotion was first observed in animals of subgroup 10B. Thereafter, tumor rates and tumor yields increased and latency periods decreased progressively in the B-subgroups with the postponenment of initiation to later fetal periods. Day 19 of prenatal development proved to be the most sensitive period to transplacental initiation, whereas initiation at day 20 led to a significant decrease in tumor rate and yield.The capability to initiate skin tumors and the extent of initiation can be correlated to both the organogenesis of the epidermis and its proliferative rate in utero.

Positive two-stage carcinogenesis in female sprague-dawley rats using 7,12-dimethylbenz(a)anthracene (DMBA) as initiator and 12-o-tetradecanoylphorbol-13-acetate (TPA) as promotor

In contrast to a previous report by Shubik, the validity of the 2-stage skin carcinogenesis experiment was demonstrated in the rat. The modified experiment was carried out in female Sprague-Dawley rats using intragastrically administered DMBA as a carcinogen and the topically applied phorbol ester TPA as a promoter. Seven groups of animals were used. Two groups were treated with TPA only, two groups were initiated only with DMBA, two further groups were both initiated and promoted, and one group served as a control. Each of the initiated/promoted groups or only initiated or promoted groups contained one sub-group in which the animals had been bilaterally ovarectomized prior to the experiment. Hyperplasia of the dorsal epidermis occurred only in the promoted and in the initiated/promoted groups. Tumors of the back skin were observed exclusively after initiation/promotion. Ovarectomy — leading to a prolonged survival time of the animals — seems to be crucial for the manifestation of malignant skin tumors. Initiation/promotion also gives rise to tumors of the forestomach, the small intestine, the liver and the colon. Tumors in other organs (especially in the mammary gland and the Zymbal gland) were also be observed after initiation alone.

Spontaneous tumors and lifespan of female NMRI mice of the outbred stock sut: NMRT during a lifetime study

SummaryA group of 150 female NMRI mice of the outbred stock Sut: NMRT was kept until they died naturally, at which time they were necropsied and examined histologically for spontaneous tumors. The natural life expectancy (median) was 782 days. Life expectancy was markedly reduced by mammary and pulmonary adenocarcinoma, and by tumors of the hypophysis. The spontaneous tumor rate was 58%. That is to say, 87 of the 150 mice had spontaneous tumors: 57 animals each had one tumor, 20 animals each had two tumors, and 10 animals each had three tumors. The organs most commonly affected by tumors were those of the lymphoreticular and haematopoietic systems, followed by the respiratory tract in second place and the breast in third place. Data reported in the literature generally show the same organ distribution, but the total tumor rate given is generally somewhat lower as the animals are seldom left alive until they die naturally (spontaneously).

Effect of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate and its nonpromoting analogue 4-O-methyl-TPA on dorsal dermal melanocytes of the Syrian golden hamster (Mesocricetus auratus)

SummaryThe effect of the tumor promoter TPA and its inactive structural analogue 4-O-methyl-TPA on the induction of dorsal skin melanosis in the normal Syrian golden hamster and on the promotion of melanomas in DMBA-initiated animals was investigated. Both phenomena were observed in TPA-treated hamsters but could not be detected after exposure of animals to 4-O-methyl-TPA. In contrast to results obtained with a variety of other laboratory animals, neither TPA nor 4-O-methyl-TPA were able to induce epidermal hyperplasia of hamster dorsal skin.

Electrolyte and glucose metabolism in VX-2 carcinoma of the rabbit

Biochemical and other parameters in VX-2 carcinoma in rabbits were evaluated. VX-2 carcinoma not only produced hypercalcemia but also hypophosphatemia and 25-OH-vitamin D deficiency. An increased turnover of 25-OH-vitamin D seems likely. Serum parathyroid hormone and urinary cyclic AMP did not increase. Hypokalemia occurred in association with hypophosphatemia and lowered blood glucose within 1 week after tumor transplantation. At the end of the experiment glucose and insulin were both below the control range. It is concluded that VX-2 carcinoma in rabbits yields much more complex biochemical alterations than reported before on calcium metabolism.