Neoplasms in rats and mice fed butylurea and sodium nitrite separately and in combination.

In projected 485-day studies, Fischer 344 rats and C57BL/6 mice were fed 0.58% butylurea and 0.50% sodium nitrite mixed in the diet separately or in combination. The number and type of neoplasms were not significantly increased in either species receiving butylurea or sodium nitrite only. Feeding the two chemicals simultaneously induced neoplasms of the lung, Zymbal's gland, forestomach, intestine and hemopoietic tissues in rats, and malignant lymphomas in mice. The increased incidence of neoplasms in rats and mice fed butylurea and sodium nitrite in combination may result from in vivo formation of the carcinogen, N-butyl-N-nitrosourea.

Physiological modification of alkylating-agent induced mutagenesis. I. Effect of growth rate and repair capacity on nitrosomethylurea-induced mutation of Escharichia coli.

The effects of repair capacity and growth rate on the induction of mutations by N-methyl-N-nitosourea (MNUA) was investigated using the trpE reversion system of Escherichia coli WP2 and some repair-deficient derivatives isogenic for this gene. In all these strains reducing the growth rate prior to MNUA-treatment caused a reduction in the mutational response, however major differences were observed between strains. In exrA and recA- bacteria stationary phase cells were 100 times less mutable than cells grown at a mean generation time (m.g.t.) of 30 min, whereas reductions of 12 and 25 times were observed in the uvrA- and wild-type strains respectively. In contrast the mutational response of the polA- mutant varied only slightly with growth rate; the increases at high MNUA concentrations being equal to the increase in the trpE gene number. These results show the increasing importance of the error-prone exrA+/recA+-dependent repair system in mutation-induction by MNUA as the growth rate of the culture is reduced and its relative unimportance for mutation induction in nutrient broth-grown cells (m.g.t. 30 min).

[Induction of tumours by different endogenously formed N-nitroso-ureas in the hooded rat (author's transl)]. / Tumorinduktion durch verschiedene endogen gebildete N-Nitroso-Harnstoffe bei der Haubenratte

By means of application of methyl-, ethyl-, n-propyl-, iso-propyl- and n-butylurea together with sodium nitrite the formation of corresponding carcinogenic N-nitroso compounds is demonstrated. The transplacental action of endogenously formed ethylnitrosourea led to a characteristic spectrum of tumours in the offspring comprising mainly neurogenic neoplasms of the brain and Nn. trigemini. The tumour incidence is especially high after application of precursors (ethylurea and nitrite) with the food. In postnatal experiments with methylurea and nitrite, there were induced mostly neurogenic tumours and reticulum cell sarcomas of the paracoecal region. A similar spectrum of tumours was found after postnatal application of iso-propylurea and nitrite by gastric tube. After a single dose of iso-propylurea and nitrite at day 21 of pregnancy there seems to be a slight carcinogenic effect in a small group of animals. The application of n-propylurea and n-butylurea, resp., together with nitrite led mainly to reticulum cell sarcomas of the paracoecal region after formation of corresponding alkylnitrosoureas. The spectrum of tumours is compared with that after the action of complete carcinogen and with the results obtained by other authors.