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c mice treated orally with methyltestosterone
46s
136
ESTRADIOL 176 CONCENTRATION IN THE QUAIL MAGNUM DURING SEXUAL DEVELOPMENT. RELATION WITH THE CONCENTRATION OF CYTOPLASMIC ESTRADIOL RECEPTORS. Jean-FranGois Pageaux and Christian Laugier. Groupe de recherche en pharmacologic et cedex - France toxicologic - INSA - 406 - 20 avenue A. Einstein - 69621 VILLEURBANNE Estradiol 178 concentration and cytoplasmic estradiol binding sites were determined in the magnum of immature and developing female quail. In the immature magnum, estradiol concentration per g of tissue was 26 times higher than in the plasma or in the muscle. Early sexual development caracterized by mucosal cell proliferation without ovalbumin synthesis, was correlated with an increase in plasma and magnum concentrations of estradiol and of cytoplasmic binding sitesin the magnum. However, the ratio of binding sites concentration to that of intratissue of estradiol, and the intracellular distribution of estradiol (cytoplasm versus nucleus) were similar in immature and developing quail. The results indicate that the presence of hormone and of binding sites in the target cells of the magnum are not sufficient ot induce cell proliferation. rloreover, these results explainthe presence of progesterone receptors in the magnum of immature quails.
137
PPSNEOPLASTIC AND MEOPIASTIC LESIONS IN LIVERS OF BALB/c MICE TREATED ORALLY WITH METHYLTESTOSTERONE W. Taylor* and Milena Lesna, Departments of Physiological Sciences* and Pathology, The Medical School, The University, Newcastle upon Tyne NE1 7RU, U.K. Male and female BALB/c mice (3 months old) were treated orally with 5 mg/kg of methyltestosterone (MeT) for 10 months. Age-matched controls received no MeT. Livers were studied by standard histopathological techniques. Hepatocellular dysplasia was found in the livers of all treated animals but not in the control group. The extent and severity of the dysplasia showed a pronounced sex difference. Most of the male mice (55/78) had severe dysplasia and 23/78 showed moderate dysplasia. The corresponding numbers for the female mice were: mild, 15/67; moderate, 48/67 and severe dysplasia, 8/67. Hepatocytic nodules were found in 6/7% male mice and 7/67 female mice. A hepatocellular carcinoma was found in only one male mouse. None of these lesions corresponded to those seen in ageing rodent livers. These findings indicate that, under the conditions employed, MeT causes a preneoplastic lesion, dysplasia, to develop in livers of treated animals, but the dysplasia does not progress to fully malignant lesions except in only a small proportion of animals of each sex. Thus MeT is a weak hepatocarcinogen in mice and we suggest that this steroid is more likely to be a promoter rather than an initiator of hepatocarcinogenesis.
138
NEOPLASTIC
TRANSFORMATION
Robert
OF BALB/C 3T3 CELLS BY METABOLICALLY ACTIVATED ESTROGENS
H. Purdy, Southwest Foundation for Research and Education, P. 0. Box 28147, San Antonio, TX 78284, USA
There is increasing evidence that certain estrogens are inducers of the neoThe A-31-1-13 subclone of cultured plastic transformation of some mammalian cells.
Balb/c 3T3 cells is being used as a model system for investigating the carcinogenic potential of steroidal estrogens. Microsomal preparations from large scale cultures of these cells contain significant levels of both estrogen 2- and 4-hydroxylase activities as measured by a radioenzymatic assay for catechol estrogen formation. Both 2and I-hydroxyestradiolare more effective than estradiol as inducers of cellular transformation. The relative frequency of neoplastic transformation induced by the estrogens assayed to date parallels the relative rates of catechol estrogen formation by the microsomes. It is concluded that the oncogenic potential of an estrogen is related to its rate of catechol estrogen formation by the microsomal activating system of the target cells, rather than to its activity as a hormone. Supported by Grant CA 24629 awarded by National Cancer Institute, DHHS.
136
ESTRADIOL 176 CONCENTRATION IN THE QUAIL MAGNUM DURING SEXUAL DEVELOPMENT. RELATION WITH THE CONCENTRATION OF CYTOPLASMIC ESTRADIOL RECEPTORS. Jean-FranGois Pageaux and Christian Laugier. Groupe de recherche en pharmacologic et cedex - France toxicologic - INSA - 406 - 20 avenue A. Einstein - 69621 VILLEURBANNE Estradiol 178 concentration and cytoplasmic estradiol binding sites were determined in the magnum of immature and developing female quail. In the immature magnum, estradiol concentration per g of tissue was 26 times higher than in the plasma or in the muscle. Early sexual development caracterized by mucosal cell proliferation without ovalbumin synthesis, was correlated with an increase in plasma and magnum concentrations of estradiol and of cytoplasmic binding sitesin the magnum. However, the ratio of binding sites concentration to that of intratissue of estradiol, and the intracellular distribution of estradiol (cytoplasm versus nucleus) were similar in immature and developing quail. The results indicate that the presence of hormone and of binding sites in the target cells of the magnum are not sufficient ot induce cell proliferation. rloreover, these results explainthe presence of progesterone receptors in the magnum of immature quails.
137
PPSNEOPLASTIC AND MEOPIASTIC LESIONS IN LIVERS OF BALB/c MICE TREATED ORALLY WITH METHYLTESTOSTERONE W. Taylor* and Milena Lesna, Departments of Physiological Sciences* and Pathology, The Medical School, The University, Newcastle upon Tyne NE1 7RU, U.K. Male and female BALB/c mice (3 months old) were treated orally with 5 mg/kg of methyltestosterone (MeT) for 10 months. Age-matched controls received no MeT. Livers were studied by standard histopathological techniques. Hepatocellular dysplasia was found in the livers of all treated animals but not in the control group. The extent and severity of the dysplasia showed a pronounced sex difference. Most of the male mice (55/78) had severe dysplasia and 23/78 showed moderate dysplasia. The corresponding numbers for the female mice were: mild, 15/67; moderate, 48/67 and severe dysplasia, 8/67. Hepatocytic nodules were found in 6/7% male mice and 7/67 female mice. A hepatocellular carcinoma was found in only one male mouse. None of these lesions corresponded to those seen in ageing rodent livers. These findings indicate that, under the conditions employed, MeT causes a preneoplastic lesion, dysplasia, to develop in livers of treated animals, but the dysplasia does not progress to fully malignant lesions except in only a small proportion of animals of each sex. Thus MeT is a weak hepatocarcinogen in mice and we suggest that this steroid is more likely to be a promoter rather than an initiator of hepatocarcinogenesis.
138
NEOPLASTIC
TRANSFORMATION
Robert
OF BALB/C 3T3 CELLS BY METABOLICALLY ACTIVATED ESTROGENS
H. Purdy, Southwest Foundation for Research and Education, P. 0. Box 28147, San Antonio, TX 78284, USA
There is increasing evidence that certain estrogens are inducers of the neoThe A-31-1-13 subclone of cultured plastic transformation of some mammalian cells.
Balb/c 3T3 cells is being used as a model system for investigating the carcinogenic potential of steroidal estrogens. Microsomal preparations from large scale cultures of these cells contain significant levels of both estrogen 2- and 4-hydroxylase activities as measured by a radioenzymatic assay for catechol estrogen formation. Both 2and I-hydroxyestradiolare more effective than estradiol as inducers of cellular transformation. The relative frequency of neoplastic transformation induced by the estrogens assayed to date parallels the relative rates of catechol estrogen formation by the microsomes. It is concluded that the oncogenic potential of an estrogen is related to its rate of catechol estrogen formation by the microsomal activating system of the target cells, rather than to its activity as a hormone. Supported by Grant CA 24629 awarded by National Cancer Institute, DHHS.