Inhibitory effect of sodium ascorbate on ethylurea and sodium nitrite carcinogensis and negative findings in progeny after intestinal inoculation of precursors into pregnant hamsters.

To assess their carcinogenic effects, the ethylnitrosourea (ENU) precursors, ethylurea and sodium nitrite, [were administered to pregnant hamsters as a single intragastic] dose on day 15 of gestation, or introduced into the cecum on day 14. Since sodium ascorbate (NaASC) inhibits the biosynthesis of nitrosamides, identical doses of the precursors were given concomitantly with NaASC. Progeny of mothers treater intragastrically developed significant incidences of neurogenic tumors of the peripheral nervous system, with a predominance in females. The concurrent administration of NaASC with ENU precursors prevented carcinogenic effects in the progency, whereas the simultaneous inoculation of the precursors into the cecum produced no carcinogenic effects in the offspring.

Experimental induction of hepatomas, mammary tumors, and other tumors with metronidazole in noninbred Sas:MRC(WI)BR rats.

Metronidazole, a chemotherapeutic agent against trichomonas infection, was tested for carcinogenicity in noninbred Sas:MRC(WI)BR rats. Three groups were given the drug for life at dose levels of 0.6%, 0.3%, and 0.06% in a powdered diet. The incidence of mammary tumors (P less than 0.020) and hepatomas (P less than 0.050) increased significantly among females given the highest dose (0.6%). Also, the rates of Leydig cell tumors of the testes (P less than 0.040) and pituitary adenomas (P less than 0.040) were statistically significant among males given the highest dose (0.6%). Results are discussed in light of a possible hazard of this drug to humans.

The effect of gonadal ablation on transplacentally induced neurogenic tumors in hamsters.

The effects of gonadectomy on tumors induced transplancentally by the ethylnitrosourea precursors, ethylurea and sodium nitrite, were investigated in hamsters. The pregnant hamsters were exposed to four daily doses of ethylurea (100 mg/kg) and sodium nitrite (50 mg/kg) administered from Day 12 to 15 of pregnancy. Weaned offspring were gonadectomized when they reached the age of 5 weeks. Orchiectomized male progeny showed a multiplicity and greater frequency of peripheral nervous system tumors and of any other tumor types than did intact males or their ovariectomized and intact female siblings. The possible inhibitory effects of endogenous androgens on the development and growth of neurogenic tumors in the peripheral nervous system and the influence of an induced endocrinal imbalance on prenatally induced neoplasms are discussed.

Effects of transplacental exposure to diethylstilbestrol on carcinogenic susceptibility during postnatal life in hamster progeny.

Prenatal exposure to a single dose of diethylstilbestrol (DES) produced a significant increase in carcinogenic response of hamster progeny that were subsequently subjected to the carcinogenic stimulus of 7,12-dimethylbenz(a)anthracene (DMBA) during postnatal life. The compounds were administered according to the following schedules. The pregnant animals (second group) received a single dose of DES, 10 mg/kg, on Day 14 of gestation. Postnatally, at 6 weeks of age, the progeny were given DMBA, 25 mg/kg p.o., twice weekly for 8 weeks. The first group received DMBA at 6 weeks of age, 30 mg/kg p.o., twice weekly for 18 weeks. The progeny exposed to DES prenatally and DMBA postnatally (DES-DMBA-exposed progeny) developed a greater multiplicity of tumors per tumor-bearing animal (p less than 0.001) and higher rates of neoplasms of the reproductive tract, e.g., ovarian and uterine tumors, mammary gland and forestomach tumors, and dermal melanomas. The prenatally DES-exposed progeny also had significantly higher incidences of malignant tumors, e.g., carcinomas of the mammary gland (p less than 0.001) and carcinomas of the forestomach (p less than 0.001), than did the hamsters given DMBA alone during postnatal life. Endocrine imbalance produced by exposure in utero may heighten the sensitivity of the progeny to development of neoplasms after a challenge with carcinogenic stimuli in adult life. The significance of these experimental data to the human situation is discussed.

Lifespan carcinogenicity tests with native carrageenan in rats and hamsters.

Native carrageenan (Gelcarin), a widely used food additive, was tested for carcinogenicity in MRC rats and Syrian golden hamsters through lifespan studies. Three groups of 30 males and 30 females from these species received carrageenan at dose levels of either 5%, 2.5% or 0.5% in the diet daily for the animal's lifespan. A trend toward an increased incidence of benign mammary tumors in females and testicular neoplasms in males occurred at the median dose level (2.5%); however, the incidence of these tumors was not statistically significant. Hamsters did not develop neoplasms in response to treatment at any dose levels. From the results of this experiment, carrageenan demonstrated no carcinogenic effects in either species.

Role of hormone imbalance in transplacental carcinogenesis induced in Syrian golden hamsters by sex hormones.

Data are presented from studies on Syrian golden hamsters with the ENU precursors, EU, and NaNO2, given transplacentally and in adulthood, and with transplacentally administered DES. Hormone modification by gonadectomy of offspring prenatally exposed to ENU caused a significantly greater incidence and multiplicity of PNS neoplasms and other tumor types in orchidectomized males, compared with intact males, and in ovariectomized and intact females. That PNS tumors in gonadectomized males appeared within a significantly shorter latency period indicated that endogenously generated androgens inhibited neoplastic development. The endocrine imbalance also induced a higher incidence of neoplasia in other tissues and organs, e.g., skin melanomas, thyroid and adrenal cortex tumors, and notably gliomas in the CNS of ovariectomized female siblings. Exposure to single doses of ENU on days 12, 13, 14, and/or 15 caused PNS tumors predominantly in females and with an increased frequency in progeny treated during the final days of gestation. The spectrum of neoplasms was greater and their incidence significant in ENU-treated adult hamsters; the tumor types different from those of transplacentally treated animals (i.e., vascular, vaginal, and ovarian tumors and fore-stomach papillomas were seen). Determining factors in carcinogenesis at the time of carcinogen treatment possibly included stage of ontogenic development, degree of cell differentiation, hormone state of host, age, total dose, and duration of treatment. DES results indicated that the haster may be a useful model for reproducing lesions similar to those observed in children of mothers treated with this drug during pregnancy.

Thyroid tumours in rats and hepatomas in mice after griseofulvin treatment.

Griseofulvin, an antibiotic used to treat dermatophystosis, was tested for carcinogenicity in mice, rats and hamsters. Three groups of mice and rats were given the drug in powdered diet in alternating 5-week periods for life, at dose levels of 3.0%, 1.5% and 0.3% (mice) and 2.0%, 1.0% and 0.2% (rats). A group of mice and 3 groups of hamsters received continuous daily treatment for life with griseofulvin at 3.0%, 1.5%, 0.3% and 0.1% dose levels respectively. A significant incidence of hepatic tumours was observed at the 2 higher treatment levels in mice. Also, statistically significant rates (P less than or equal to 0.001 and/or P less than or equal to 0.020) of thyroid tumours, indicating a dose-response, were recorded in male rats at the 2.0%, 1.0%, and 0.2% dose levels, and in females at the 2.0% and 1.0% dose levels. Hamsters did not develop neoplasms in response to treatment at any level.

Ganglioneuromas in hamsters.

A description is given of three cases of ganglioneuromas, which originated from ganglia of the sympathetic chain of hamsters. Other reports of such tumors in this species are reviewed and the literature relative to hamster ganglioneuromas presented. In addition, the possible genesis of origin from adult ganglion cells upon the action of carcinogenic stimuli is discussed.

Transplacental effects of ethylnitrosourea precursors ethylurea and sodium nitrite in hamsters.

Four simultaneous dosages of the ethylnitrosourea precursors, ethylurea and sodium nitrite, were administered intragastrically to pregnant hamsters at 100 mg/kg and 50 mg/kg respectively, from the 12-15th days of pregnancy. The treatment induced multiple neurogenic tumors of the peripheral nervous system in the offspring. Female progeny developed a greater incidence and multiplicity of peripheral nervous system tumors with significantly shorter latencies than males, thus establishing evidence that the tumors were age and sex dependent. The tumors presented varied morphological patterns and upon transplantation, grew regularly, exhibiting their malignant nature. The possible influence of estrogenic hormones on the development and growth of peripheral nervous system tumors and comparative aspects of the relationship between prenatal and postnatal carcinogenesis with regard to the ensuing tumor spectra as a consequence of exposure to the same chemical agent, are discussed.