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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of prolactin, estradiol, and progesterone on 3-methyl-cholanthrene (MCA)-induced cervical carcinogenesis in the NMRI strain of mice are reported. Females were ovariectomized at 6-9 weeks of age. 1 week later cotton threads impregnated with a mixture of MCA and beeswax were inserted into the uterine cervix. In 1 group animals were injected with 5 mcg of ovine prolactin in a solvent. A 2nd group received 5 mcg of estradiol-17beta in the same solvent. A 3rd group received both prolactin and estradiol. The control group received only the solvent. Injections were started on the day of operation and given for 6 days. Some animals were killed on the day after the last injection, others 4 weeks later. In other groups progesterone was injected every 3rd day after the estradiol and progesterone injections. Animals which were killed 1 week after insertion of the MCA threads had stratified squamous epithelium with mild atypica in some areas. A few scattered epithelial ''buds'' were seen to penetrate the stroma. In estradiol-injected animals, 2 of 8 had similar ''buds'' and signs of direct stromal invasion of cells from the basal epithelial layer. In 9 animals receiving only prolactin, 2 showed ''buds'' and doubtful basal membrane invasion. In 6 of 9 animals injected with both prolactin and estradiol, larger ''buds'' were present and overt invasion was seen. In animals killed 4 weeks after operation, squamous cervical carcinomas were found significantly more frequently among animals injected with both estradiol and prolactin (p less than .001) than in other groups. Progesterone had no definite effect on the incidence of carcinoma.
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PMID:A synergistic effect of oestradiol and prolactin influencing the incidence of 3-methylcholanthrene induced cerivical carcinomas in mice. 97 Jan 26

The cyclic change of human endometrial cells are controlled by the interaction between hypothalamus, pituitary gland and ovaries, thus making the endometrium proliferate, differentiate, exfoliate and then reproduce. The menstrual cycle is divided into three phases which are called follicle, ovulatory and luteal phase by the morphological change of the ovarium. The endometrial cycle is also classified to proliferative, secretory and menstrual phase. Estradiol (E2) stimulates the proliferation of endometrial cells by the indirect positive mechanism activated by the binding of E2 to E2 receptor. Growth factors (IGF- I, EGF, TGF- alpha etc.) induced by the transcription of the gene promote the proliferation of endometrial cells. Progesterone (P) has antagonistic effects on E2 actions and transform proliferative phase to secretory phase in endometrium. It is suggested that the possible mechanism of carcinogenesis of normal endometrium is the progression of endometrial hyperplasia due to the prolonged and unphysiological exposure to E2. The additional role of oncogenes (fos, fms, myc, myb, erb-B, neu) and growth factors on the mechanism of carcinogenesis of hyperplasia to cancer is very interested.
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PMID:[The physiological function of human endometrium]. 178 83

An altered pattern of cytochrome P-450-dependent microsomal steroid metabolism was identified in female mouse liver tumors induced by 5,9-dimethyldibenzo[c,g]carbazole, a potent organo-specific liver carcinogen. These tumor tissues were compared to extratumoral liver parenchyme, to normal, fetal and neonatal livers and to spontaneous liver tumors, the frequency of which is very low in the highly hybridized mouse strain (XVIInc/Z) used for liver tumorigenesis. Cytochrome P-450-dependent steroid hydroxylase activities were measured by the identification and quantification of four monohydroxyprogesterone and eight monohydroxytestosterone metabolites. In contrast to a general decrease (50%) of total P-450 in tumor microsomes, the individual steroid hydroxylases were regulated differently. Progesterone 16 alpha- and testosterone 6 alpha-, 6 beta-, 7 alpha- and 16 alpha-hydroxylase activities were decreased 50%, and more, whereas progesterone and testosterone 15 alpha-hydroxylase activities were raised 3-4 times with regard to microsomal protein content and 6-7 times with regard to total P-450. Consequently the most prominent feature of the steroid metabolism by tumor-borne microsomes is the hydroxylation at the 15 alpha-position. Furthermore, minor testosterone 2- and 15 beta-hydroxylase activities showed equally an increase of approximately 4 times (8 times with regard to total P-450). The observed new tumoral pattern of P-450-dependent microsomal steroid metabolism appearing characteristically in spontaneous and chemically induced liver tumors indicates that particular P-450 enzymes are strongly expressed in mouse liver tumors. These enzymes may be used as markers for early stages in liver tumorigenesis.
Carcinogenesis 1989 Oct
PMID:Particular cytochrome P-450-dependent steroid metabolism: a new class of mouse liver tumor markers. 279 Dec 5

In normal breast, estrogen stimulates growth of the ductal system, while lobular development depends on progesterone. Thus, estrogen and progesterone, when secreted in an adequate balance, permit the complete and proper development of the mammary gland. Progesterone may also have an antagonistic activity against estradiol, mediated through a decrease in the replenishment of the estrogen receptor, and also through increased 17 beta-hydroxysteroid dehydrogenase which leads to accelerated metabolism of estradiol to estrone in the target organ. Thus, it can be inferred that long periods of luteal phase defect leading to an unopposed estrogen effect on the breast might promote breast carcinogenesis.
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PMID:Antiestrogen action of progesterone in breast tissue. 329 11

Oestrogen predominance over progesterone may cause hyperproliferation of mammary epithelium and thus promote breast carcinogenesis. In patients with a hormone-dependent tumour, oestrogens may also accelerate cancer growth. Conversely, they may inhibit tumour growth in patients with an oestrogen receptor-negative carcinoma which has grown in an oestrogen-poor environment. Progesterone opposes oestrogen-induced epithelial proliferation and causes cellular differentiation with decreased mitosis, thus reducing the risk of breast cancer. Prolactin brings about mammary epithelial differentiation for secretory function; in the lactation state, epithelial proliferation is minimal. The role of androgens, melatonin, thymosin, metabolic hormones (growth hormone, thyroid hormone(s), insulin, glucocorticosteroids) and prostaglandins in the pathobiology of breast cancer is poorly understood. A breast cancer population consists of individuals in whom more than 20 different tumour subsets may be present, i.e. patients with different individual tumour pathobiology and endocrinology patterns and therefore different prognoses. Progress in the endocrinology of breast cancer seems possible through prospective studies in which hormones are determined in normal breast tissue (ductal fluid, cyst fluid) and then related to the corresponding concentrations in the plasma and urine of patients who develop breast cancer and those who do not. In addition, genetic and nonhormonal risk factors for breast cancer must be taken into consideration to define the endocrinological aspects involved.
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PMID:Endocrinology of breast cancer. 330 71

The effect of carcinogenesis on various hepatic microsomal parameters and related cell functions was studied in two tumor models. Hepatocarcinoma was produced by diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) (Solt-Farber model) and mammary adenocarcinoma using R3230 AC cancer cell line. In these models the effect of the tumor on metabolic functions of hepatocytes was studied. In the DEN/2AAF tumor model in nodules phase I components (cytochrome P-450, aminopyrine N-demethylase, arylhydrocarbon hydroxylase) were reduced, together with microsomal progesterone content and total and specific progesterone binding. Phase II components (glutathione, glutathione S-acyltransferase, UDP-glucuronyl transferase, epoxide hydrolase) were increased. In hepatoma the effects were more enhanced. Nodules grown in the speen retained the dedifferentiated enzyme characteristics. In the R3230 AC mammary adenocarcinoma phase I components of the hepatic endoplasmic reticulum were reduced, and phase II components increased. Progesterone content and receptor binding were also increased. These results indicate that enzymatic abnormalities in the liver cell are connected with cancer production and the hepatic dedifferentiation seems to be indistinguishable in tumor-bearing liver from those seen with extrahepatic neoplasms.
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PMID:Hepatic metabolism and carcinogenesis. Its role in hepatoma and adenocarcinoma. 338 80

In most target cells of the female genital tract, adequate cell differentiation is obtained via the successive and synergistic actions of estradiol (E2) and progesterone (P). This mainly due to the fact that progesterone receptor (PR) synthesis involves the prior action of estradiol through its receptor (ER). In normal breast, E2 stimulates the growth of the ductal system whereas lobular development depends on progesterone secretion. In other words E2 + P, when secreted in an adequate balance, permit the complete and proper development of the mammary gland. On the other hand progesterone may also have an antagonistic action against E2. The antiestrogen activity of progesterone is mediated through a decrease in the replenishment of E2 receptor and the synthesis of 17 beta-hydroxysteroid dehydrogenase, which leads to an accelerated metabolism of E2 to E1 in the target organ itself. These biochemical events, which have been well documented in the endometrium, have also been shown in cultures of normal breast epithelial cells as well as in differentiated fibroadenomas with high cellular density. In addition, data from the literature show that E2 added to human breast cells increases cell multiplication by means, eventually, of the synthesis of growth factors. Progesterone and progestins have a reverse effect. Data from our laboratory indicate that in normal cultured cells E2 and progestins are also antagonists with regard to cell multiplication. From these different data, it is postulated that in human beings, long periods of a luteal-phase defect leading to an unopposed estrogen effect might be a promoter of carcinogenesis in the breast.
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PMID:Estradiol/progesterone interaction in normal and pathologic breast cells. 352 47

Hepatocyte nodules that persist throughout chemical carcinogenesis are linked to carcinomas both as one site at which hepatomas are seen to arise and as a tissue which shows more than a dozen significant protein changes also found in liver cancers. In view of the differential stimulus to growth of these persistent nodules by progesterone, progesterone metabolism and binding to the microsomes of nodules and hepatomas were studied. Progesterone metabolizing enzyme activities in nodule microsomes showed striking shifts with a 42% decrease in 16 alpha-hydroxylase activity and a 2- to 3-fold increase in 6 beta-hydroxylase activity compared to control levels. Hepatomas had a dramatic 20-fold increase relative to nodules or controls in the reductive pathway for progesterone metabolism as measured by delta 4-5 alpha-hydrogenase activity. The rate and saturation of the specific binding of progesterone to microsomes of nodules and liver cancers were significantly decreased when compared either to the tissue surrounding the nodules or to their respective control microsomes. This change in progesterone binding of nodular microsomes may relate to an altered balance of progesterone content and its metabolites in the nodular cells or to alterations in the microsomal membrane binding site. The functional significance of reduced binding of progesterone for liver carcinogenesis is thus open to further inquiry.
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PMID:Changes in progesterone binding and metabolism in liver microsomes from persistent hepatocyte nodules and hepatomas in male rats. 394 Feb 12

This is a review of known periods in utero during which drugs alter the process of growth; effects may be shown on the fetus or the newborn and vary with the stage of development of the fetus when exposed. Other variables are the mother and the placenta. There is no safe animal screening mechanism, the human test is by ordeal, and more clinical monitoring and reporting are needed. Cancer chemotherapeutic agents exert their maximal effects on rapidly dividing cells and are therefore hazardous during pregnancy; the greatest risk is in the 1st trimester. In the thalidomide experience the critical days were the 22nd and 23rd days after conception. Masculinizing drugs such as testosterone and other androgenic steroids have been implicated as affecting the female fetus when given early in pregnancy. Oral contraceptives taken by an already pregnant woman are a hazard because of these progestational agents. Progesterone alone is unlikely to cause masculinization but other progestins may cause such changes. Carcinogenesis may develop later in females born of mothers who are treated with diethylstilbestrol to prevent miscarriage. Many antithyroid drugs have caused neonatal goiter. Maternal ingestion of iodides during pregnancy (preparations for treating asthma, cough syrups, radio-contrast media used in diagnoses) is the most frequent cause. Goiter is relatively common in infants whose mothers were treated with propylthiouracil and other antithyroid drugs, yet they usually show normal thyroid function. However, hypothyroidism with cretinism can occur. Lithium, used in psychiatry and as a salt substitute, may alter iodine metabolism and thyroid gland function. It also passes into the milk to continue the potential toxicity. Teratogenic effects in experimental animals suggest other possible effects on infants from lithium and similar drugs.
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PMID:Human experiences related to adverse drug reactions to the fetus or neonate from some maternally administered drugs. 414 Jun 79

The binding of 125I-labelled epidermal growth factor (EGF) was utilized to monitor possible cell surface effects of polycyclic aromatic hydrocarbon carcinogens. Exposure of confluent C3H 10T1/2 mouse fibroblasts to 1 muM benzo[a]pyrene led to a time-dependent decrease of EGF binding. By 24 h, EGF binding was only 5% that of control cultures. In contrast, benzo[a]pyrene-7,8-diol-9,10-oxide did not significantly alter EGF binding, indicating that the inhibition by benzo[a]pyrene was not simply due to DNA damage. A curvilinear Scatchard plot in the control cells was consistent with the presence of two classes of EGF receptors having differing affinities. Our results suggest that the major effect of benzo[a]pyrene was a reduction in receptor number rather than affinity, although other interpretations have not been excluded. Progesterone, 17 beta-estradiol, benzo[e]pyrene, cholesterol, phenobarbital, 1,1-bis-(p-chlorophenyl)-2,2,2-trichloroethane, hexachlorobenzene or pregnenolone-16 alpha-carbonitrile, did not inhibit EGF binding. On the other hand, several known inducers of P1-450 were very effective inhibitors of EGF binding. These included: dimethylbenz[a]anthracene, 3-methylcholanthrene, benzo[a]pyrene, benz[a]anthracene, beta-naphthoflavone and alpha-naphthoflavone. We postulate that the binding of certain polycyclic aromatic hydrocarbons to the Ah receptor may induce not only specific drug metabolizing enzymes but also inhibition of EGF binding, and possible other cell effects. Further studies are required to verify this hypothesis.
Carcinogenesis 1982
PMID:Benzo[a]pyrene and other inducers of cytochrome P1-450 inhibit binding of epidermal growth factor to cell surface receptors. 628 2


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