[Effect of high dietary fat on the total DNA and receptor contents in rats with 7,12-dimethylbenz[A]anthracene-induced mammary carcinoma].
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The influences of high dietary fat on the malignant intensity and the hormone receptors of DMBA-induced mammary breast carcinoma were analyzed in female Sprague-Dawley rats. The rats were fed either a low-fat diet or high-fat diet after the DMBA administration. As the results, incidence, size, average latent period, DNA histogram, DNA index and % of S-phase fraction of tumor were significantly different between both groups. But the ER and PgR contents were not different between both groups. The results suggest that a high dietary fat could increase the malignant intensity of the tumor but does not influence the receptor contents of the tumors.Keywords:
7,12-Dimethylbenz[a]anthracene
Mammary carcinoma
Mammary tumor
Dietary fat
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The treatment of rats with DMBA-induced mammary tumours with vitamin A and hormones in the cyclic regime increases the lifetime of animals, decreases both the tumour growth rate and increases the degree of their differentiation. The treatment with vitamin A alone and in combination with hormones lowers the level of estradiol and progesterone receptors in the rat mammary tumours. The high frequency of receptor-positive tumours and high level of estradiol and progesterone receptors in them were observed under the influence of hormones alone in the cyclic regime.
Mammary carcinoma
Mammary tumor
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Mammary tumors induced in female rats by repeated gastric instillations of 3-methylcholanthrene grow more rapidly than tumors induced by single gastric instillations of 7,12-dimethylbenz ( a ) anthracene. Over a 6-week period, the inhibition of tumor growth by ovariectomy or by estradiol benzoate is more evident by inhibition of tumor weight of the MCA tumors, but complete regressions occur more frequently with DMBA tumors.
Mammary tumors appearing in female rats after administration of carcinogenic polycyclic hydrocarbons are used for the evaluation of cancer chemotherapeutic agents. The tumors are partially hormonedependent and in other ways are considered to resemble mammary carcinoma in humans.
Two experimental systems have been most popular. The 1st uses female Wistar rats that receive repeated gastric instillations of 3-methylcholanthrene (MCA), a method introduced by Shay and his coworkers (8) in 1949. The 2d system uses female Sprague-Dawley rats that are given single doses of 7,12-dimethylbenz( a )anthracene (DMBA), the method introduced by Huggins et al. (7) in 1961.
Few studies have compared systematically the appearance and behavior of mammary tumors induced by these 2 methods. We have reported one such study (6), and showed that the Sprague-Dawley rat is more susceptible than the Wistar rat to the induction of mammary tumors after gastric instillations of both carcinogens, as expressed in a greater proportion of animals that develop tumors, shorter mean time of appearance of such tumors, and a greater number of tumors per rat. These data are summarized in Table 1.
The same study (6) also revealed that the mammary tumors induced by repeated administrations of MCA grew significantly more rapidly than the tumors induced by single doses of DMBA, as expressed by the mean diameter of the masses on Day 30. There was no difference in growth in the 2 strains of rats. These data, recalculated as the mean volume of tumor per rat 21 days after appearance, are given in Table 2.
Tumors induced by multiple administrations of MCA in Wistar rats have been used in this laboratory in a series of studies that tested over 100 hormonal and nonhormonal chemicals (1,2,4,5). Tumors induced by single doses of DMBA in Sprague-Dawley rats have been used in similar investigations by Griswold et al. (3) and Teller et al. (9). We (4) suggested that the difference in the growth rate, as well as the difference in the effect of MCA and DMBA on the hormonal status of the host, could affect the therapeutic response (4). A direct comparison of the response of MCA- and DMBA-induced tumors to several chemotherapeutic agents appeared desirable, and such an experiment was started.
This report compares the growth of mammary tumors in female Wistar and Sprague-Dawley rats that received MCA or DMBA, and the response of such tumors to ovariectomy, estradiol benzoate (NSC-9566) and dromostanolone propionate (NSC-12198).[3][1]
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7,12-Dimethylbenz[a]anthracene
Methylcholanthrene
Mammary tumor
Mammary carcinoma
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7,12-Dimethylbenz[a]anthracene
Mammary carcinoma
Mammary tumor
Alpha (finance)
Thymosin
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We investigated the effects of a high-fat diet and indomethacin on tumorigenesis, tumor proliferation and cell kinetics of 7,12-Dimethylbenz(a)anthracene (DMBA)--induced mammary carcinomas in Sprague-Dawley (SD) rats. Both the high-fat diet and indomethacin significantly stimulated tumor proliferation and cell kinetics, whereas tumorigenesis was significantly stimulated by the high-fat diet but it was significantly inhibited by indomethacin. Moreover, switching the animals from the high-fat diet with or without indomethacin to the low-fat diet suppressed tumor proliferation and cell kinetics. It can therefore be concluded that either a high-fat diet or indomethacin stimulates tumor proliferation in DMBA--induced mammary carcinoma in SD rats.
7,12-Dimethylbenz[a]anthracene
Mammary carcinoma
Mammary tumor
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Summary Long-Evans female rats show a smaller mammary neoplastic response than do Sprague-Dawley females to 7,12-dimethylbenz(α)anthracene (DMBA) applied directly to mammary tissue in vitro when the excised mammary tissue is grafted back into the animal from which it came. Long-Evans rats also give a smaller mammary neoplastic response to DMBA administrated by stomach tube. It was suggested that the difference in the mammary neoplastic response to DMBA observed in the 2 strains depends upon strain differences that act after the initial DMBA-mammary tissue interaction.
7,12-Dimethylbenz[a]anthracene
Mammary tumor
Stomach tube
Mammary carcinoma
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To study the biological characteristics of 7, 12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in rats, 20 Sprague Dawley female rats received a single oral dose of 5 mg of this carcinogen. During the 35-week observation time 78 primary tumors were removed. While in most cases the primary tumor could be removed completely, 7 out of 20 animals eventually had to be sacrificed for inoperable local recurrence of the primary tumor. Notwithstanding, the long period of time given for tumor metastases to develop (mean time between tumor removal and termination was 18.5 weeks), tumor spread either to lungs or regional lymph nodes could not be established. This relatively benign behavior of the tumor was in contrast with the morphological characteristics of the tumor, which uniformly showed the features of adenocarcinomas. The difference in biological behavior between DMBA-induced mammary tumors in rats and malignant mammary tumors in humans suggests that as a model this system is of limited value for investigations of mechanisms of malignant behavior of human tumors.
Mammary tumor
7,12-Dimethylbenz[a]anthracene
Primary tumor
Mammary carcinoma
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Summary A semisynthetic high-corn oil diet enhanced the development of mammary cancer induced by 7,12-dimethylbenz(α)anthracene (DMBA) in intact female Sprague-Dawley rats. This was in comparison to two other groups of similarly treated rats fed a high-coconut oil and a low-fat semisynthetic diet, respectively. The average daily caloric intake was similar, and the average growth rate, based on body weight, was comparable in all three groups. Fatty acid analyses demonstrated that, at the time of DMBA administration, the composition of mammary fat was different in the three different groups, reflecting their dietary fat intake. The data from this study suggest that dietary effects upon DMBA mammary carcinogenesis were related to the nature as well as the amount of fat used.
Dietary fat
7,12-Dimethylbenz[a]anthracene
Corn oil
Coconut oil
Mammary tumor
Caloric intake
Mammary carcinoma
Sesame oil
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The influences of high dietary fat on the malignant intensity and the hormone receptors of DMBA-induced mammary breast carcinoma were analyzed in female Sprague-Dawley rats. The rats were fed either a low-fat diet or high-fat diet after the DMBA administration. As the results, incidence, size, average latent period, DNA histogram, DNA index and % of S-phase fraction of tumor were significantly different between both groups. But the ER and PgR contents were not different between both groups. The results suggest that a high dietary fat could increase the malignant intensity of the tumor but does not influence the receptor contents of the tumors.
7,12-Dimethylbenz[a]anthracene
Mammary carcinoma
Mammary tumor
Dietary fat
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Corticosterone
7,12-Dimethylbenz[a]anthracene
Hypothalamic–pituitary–gonadal axis
Gonadotropin
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