Caffeine inhibits development of benign mammary gland tumors in carcinogen-treated female Sprague-Dawley rats.

The purpose of this study was to assess the influence of caffeine on the incidence of benign mammary tumors in carcinogen (DMBA) treated female Sprague-Dawley rats. Four different animal models were used in these studies, i.e., the administration of DMBA to: [1] 55 day old virgin rats; [2] 53 day old ovariectomized, estrogen treated virgin rats; [3] 135 day old virgin rats and [4] 135 day old parous rats. A high incidence of benign mammary fibroadenomas was observed in each of the four animal models. In addition, in the estrogen treated ovariectomized animals, a high incidence of secretory mammary gland cysts was observed. Caffeine (500 mg/L drinking water) was administered daily throughout the study commencing 3-31 days after carcinogen treatment. Caffeine treatment significantly (P less than 0.05 to P less than 0.001) reduced the incidence of benign mammary fibroadenomas in the 55 day old virgin rat model (P less than 0.01), in the 53 day old estrogen treated ovariectomized virgin rat model (P less than 0.05 to P less than 0.001) and in the 135 day old virgin rat model (P less than 0.05). The number of benign mammary fibroadenomas was reduced by caffeine in the 135 day old parous rat model but this reduction was not significant (P less than 0.10). In addition, in the estrogen treated ovariectomized virgin rat model, caffeine significantly (P less than 0.05 to P less than 0.001) reduced the incidence of mammary gland cysts. Caffeine treatment either increased or had no significant effect on body weight gains, depending upon the animal model.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemoprevention of 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis in rat by the combined actions of selenium, magnesium, ascorbic acid and retinyl acetate.

The chemopreventive actions of sodium selenite (SS), magnesium chloride (MC), ascorbic acid (AA) and retinyl acetate (RA), given singly or in combinations, on mammary carcinogenesis induced by 30 mg of 7,12-dimethylbenz[a]anthracene (DMBA) in female adult rats were evaluated. Administration of modulators was carried out from the age of 40 +/- 3 days to 240 +/- 3 days. When DMBA alone was given 100% of the rats developed mammary tumors. When modulators were given singly the tumor incidences were reduced to 51.77% (SS), 46.4% (MC), 57.1% (AA) and 48.1% (RA). When the modulators were given in combination of twos, the tumor incidences were further reduced to 29.5% (SS + MC), 31% (SS + AA), 29.6% (SS + RA), 25.9% (MC + AA), 31.8% (MC + RA) and 34.6% (AA + RA). Administration of modulators in combinations of threes resulted in still further reduction of tumor incidences to 22.2% (SS + MC + AA), 19.2% (SS + MC + RA), 16% (MC + AA + RA) and 23.1% (AA + RA + SS). When all four modulators were given concurrently the tumor incidence was only 12%. Further, the number of tumors per tumor-bearing animal declined with the increase in the number of agents used in combination for modulation.

[Importance of early diagnosis in the improvement of prognosis in breast carcinoma: non-palpable lesions. Preliminary results]. / Importanza della diagnosi precoce per il miglioramento della prognosi del carcinoma mammario: le "lesioni non palpabili". Risultati preliminari.

There are still marked differences in the current indications for breast screening proposed by the various international school of oncology. Epidemiological data to the effect that breast screening in asymptomatic women aged over 50 reduces the death rate due to breast cancer now appears to be widely accepted, but an analogous finding for women aged between 40-49 has not yet been confirmed. Following a brief analysis of the most important breast screening programmes carried out to date, the Authors report the preliminary results regarding the identification and biopsy of non-palpable breast lesions during the course of a screening programme in 1986 by the Dept. of Cancer Surgery. Of a total of 1128 breast scans in asymptomatic patients aged between 40 and 73, 24 suspect (1.9%) non-palpable lesions were found of which 5 (20.8%) proved to be carcinomas.

Effect of moderate vitamin A supplementation and lack of dietary vitamin A on the development of mammary tumors in female rats treated with low carcinogenic dose levels of 7,12-dimethylbenz(a)anthracene.

We examined the effect of moderately increased and of marginal continued dietary supplementation of vitamin A (retinyl acetate) and the effect of lack of dietary vitamin A on the initiation and promotion stages of mammary tumorigenesis in female Sprague-Dawley rats treated with a single low (0.5 mg/100 g body weight) or very low (0.1 mg/100 g body weight) dose of i.v.-administered 7,12-dimethylbenz(a)anthracene. The number of mammary tumors was significantly (P less than 0.05) reduced if prior to and during initiation with 7,12-dimethylbenz(a)anthracene the rats were fed a moderately increased (30 micrograms/day) or marginal (3 micrograms/day) amount of vitamin A, compared to rats fed an adequate (10 micrograms/day) amount of vitamin A. The number of mammary tumors was also significantly (P less than 0.05) reduced when a moderately increased or marginal amount of vitamin A was provided during the tumor promotion phase. In addition, the number of mammary tumors was significantly (P less than 0.05) reduced by the lack of dietary vitamin A during both the initiation and promotion stages of this tumorigenic process, when compared to vitamin A adequate, ad libitum-fed rats, but not when compared to vitamin A adequate, food-restricted controls. The reduction in numbers of mammary tumors observed in these studies was reflected primarily in significant (P less than 0.05) decreases in mammary fibroadenomas; the number of mammary carcinomas was often reduced, but due to a low frequency of the carcinomatous lesions, this reduction did not reach the 5% level of statistical probability. Plasma and liver vitamin A levels were determined during both the initiation and promotion stages. As the dietary supplementation of vitamin A increased from 0 to 30 micrograms/day, there was an increase in mean liver and plasma vitamin A levels. No consistent correlation between plasma and liver vitamin A levels and the occurrence of mammary tumors was observed, except with the moderately increased (30 micrograms/day) intake of vitamin A, that resulted in a small, but statistically significant (P less than 0.05) increase of serum retinol at initiation; this may account for the observed reduction in mammary tumors. These results provide evidence that moderate alterations in vitamin A consumption can modulate low-dose chemically induced mammary gland tumorigenesis. Most importantly, suppression of mammary gland tumorigenesis can be achieved by moderately increased, frequent, and regular consumption of vitamin A; prolonged consumption of vitamin A-deficient diets or diets marginal in vitamin A does not enhance the risk of mammary tumor development.

Inhibition of chemically induced mammary carcinogenesis in rats by short-term exposure to butylated hydroxytoluene (BHT): interrelationships among BHT concentration, carcinogen dose, and diet.

Dietary butylated hydroxytoluene (BHT) fed 14 days before and 14 days after carcinogen administration resulted in a dose-dependent inhibition of 7, 12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor incidence in outbred Sprague-Dawley rats. In addition, the inhibitory effects of BHT were strongly influenced by the dose of initiating carcinogen and the type of diet in which BHT was administered. In animals fed the NIH-07 diet and receiving a low dose of DMBA (5 mg/rat), the inhibitory effect of BHT was manifested at all four BHT concentrations (6,000 leads to 300 ppm). Maximal inhibition was approximately 50% in animals given 5 mg DMBA and receiving 6,000 ppm BHT. However, in the group administered a high dose of DMBA (15 mg/rat), the inhibitory effect of BHT was expressed only at 6,000 ppm, the highest concentration given. Lower concentrations (300 and 1,000 ppm) of BHT had no detectable effect on tumor incidence. In animals fed the defined, semipurified AIN-76A diet during the 4-week treatment period and initiated with 5 mg DMBA, BHT at 6,000 ppm inhibited tumor development. However, at 15 mg DMBA animals fed the AIN-76A diet differed markedly from those fed the NIH-07 diet. In the former group, BHT at 6,000 ppm was unable to elicit any inhibitory response; in the latter group, BHT inhibited tumor development by 40%. Dietary BHT also inhibited DMBA-induced adrenocortical hyperplastic nodules in a dose-dependent fashion. These results indicate that short-term exposure to dietary BHT can inhibit experimental mammary tumor development at environmentally relevant concentrations.

Effect of selenium on the induction of breast fibroadenomas by adenovirus type 9 and 1,2-dimethylhydrazine-induced bowel carcinogenesis in rats.

Selenium in its organic and inorganic forms has been shown to inhibit the development of chemically induced, spontaneous and transplanted tumors. The present investigation was performed to study the effect of selenium (4 micrograms per ml of drinking water) on tumorigenesis of adenovirus-type-9-induced breast fibroadenomas and on 1,2-dimethylhydrazine-induced bowel carcinogenesis in WF rats. It was found that identical treatment with Se under identical conditions and with no obvious toxic effects on the rats (1) resulted in inhibition of DMH-induced large-bowel carcinogenesis; (2) facilitated induction of small-bowel cancer by the same carcinogen in the same animals, and (3) greatly facilitated induction of breast fibroadenoma by adenovirus type 9 in the same strain of rats. The effect of Se treatment on DMH-induced large-bowel carcinogenesis confirms previous findings and proves that the opposite effect on fibroadenoma development is not due to differences in e.g. effective dose, animal strains or condition of the animals. It is not yet clear through which mechanisms Se exerts these effects.

[Inhibition of the growth of 7,12-dimethylbenz(a)anthracene- and N-nitrosomethylurea-induced mammary gland neoplasms by methionine in rats]. / Tormozhenie metioninom razvitiia raka molochnoi zhelezy, indutsirovannogo 7,12-dimetilbenz(a)antratsenom i N-nitrozometilmochevinoi u krys.

The diets supplemented with 0.5% methionine inhibited the development of mammary adenocarcinomas induced in female rats with 7,12-dimethylbenz(a)anthracene and N-nitrosomethylurea by 3.8 and 2.3 times, respectively. Methionine produced no effect on the incidence of other new-growths. It is suggested that the mechanism by which methionine exerts an antineoplastic effect on mammary carcinomas is a consequence of its hypolipidemic and neurotropic activity.

[Inhibition of the blastomogenic effect of 7,12-dimethylbenz(a)anthracene in female rats by buformin, diphenin, a polypeptide pineal extract and L-DOPA]. / Tormozhenie buforminom, difeninom, polipeptidnym ékstraktom épifiza i L-DOFA blastomogennogo éffekta 7,12-dimetilbenz(a)antratsena u krys-samok.

Female rats were treated with buformin, phenytoin, polypeptide pineal extract, L-DOPA or buformin combined with L-DOPA during 3 weeks before intravenous injections of DMBA (1.5 mg 6 times with one-week intervals) over a period of carcinogen injections and after it till the animals' death. The overall tumour incidence in the control group was 97%, while in buformin, phenytoin, pineal extract, L-DOPA and buformin + L-DOPA treated groups it amounted to 55, 71, 80, 50 and 62%, respectively (P < 0.05). The incidence of mammary adenocarcinoma amounted to 81, 36, 55, 26, 25 and 19%, respectively (P < 0.05). The mechanisms of the similar effects the drugs belonging to different classes produce on chemical carcinogenesis are discussed.

Fibroadenoma in oral contraceptive users: a histopathologic evaluation of epithelial atypia.

We have reviewed histologically a series of 120 fibroadenomas which formed part of the case material from a previous case-control epidemiological investigation of the relationship between oral contraceptive use and breast disease. We evaluated the epithelial component of the fibroadenoma for degree of cytologic atypia. This study indicates that the reduced risk for fibroadenoma among long-term users of oral contraceptives does not vary according to the degree of epithelial atypia present. This is in contrast to our previously reported findings for fibrocystic disease, in which the decreased frequency of occurrence of the disease in long-term users of oral contraceptives was found only for cases with no minimal epithelial atypia.

Inhibition of mammary carcinogenesis of dimethylbenzanthracene treated rats with a brominated triphenylethylene.

Daily administration of a brominated triphenylethylene (TBP), to rats which received 20 mg of DMBA p. o. inhibits mammary carcinogenesis. The effect appears even with very small doses (i ppm in the diet) and seems to be dose related. With one exception (an adenofibroma) the tumours in control and treated animals were malignant. Administration of TBP prevents the appearance of corporea lutea in the ovaries but not the usual necrosis of the adrenal cortex.

Oral contraceptives and breast neoplasia.

The continued high prevalence of oral contraceptive (OC) use by young women warrants the careful study of these agents. At present, it appears that the risk of benign breast disease is reduced by use of OCs. This effect seems to be greater for fibrocystic disease than for fibroadenoma. Available information suggests that, as yet, OC use has not had any effect on breast cancer risk. The recent slight rise in breast cancer rates in younger women has not been shown to be due to OC use. The relationship between OCs and breast cancer may not become clear for another 5 to 10 years because of the long latent period of this disease. Meanwhile, for reasons presented, it would seem wise not to prescribe OCs for women with a history of benign breast disease and to withdraw them from women who develop these conditions.

Inhibitory effect of L-arginine on growth of rat mammary tumors induced by 7,12-dimethylbenz(a)anthracene.

The effect of L-arginine on growth of rat mammary tumors induced by 7,12-dimethylbenz(a)anthracene was studied. Growth of induced tumors was inhibited by feeding rats an arginine-enriched diet containing 5% L-arginine in addition to the necessary components for rats, including 15% milk casein. The diet significantly reduced both the rate of tumor induction and the number of tumors induced per rat. Histological examination showed that the tumors induced were more benign in rats fed the arginine-enriched diet than in those fed the control diet. A possible mechanism of the inhibitory effect of L-agrinine id discussed.