Showing papers on "7,12-Dimethylbenz[a]anthracene published in 1979"

Relationship between amount and type of dietary fat in promotion of mammary carcinogenesis induced by 7,12-dimethylbenz[a]anthracene.

Abstract: Female Sprague-Dawley rats were fed semipurified diets containing various fats, either alone or in combination, to provide different amounts of dietary fat and linoleic acid. One week before commencing the diets, each rat received an intra-gastric dose of the carcinogen 7,12-dimethylbenz[a]anthracene. Rats fed diets containing mixtures of 3% sunflower seed oil and 17% of either tallow or coconut oil developed twice as many tumors as those fed 3% sunflower seed oil or 20% of either saturated fat alone. Tumor yields in the rats fed these mixed-fat diets were comparable to those in rats fed a 20% lard diet, which provided about the same amount of linoleic acid. No further increase in tumor yield was observed in rats fed a 20% sunflower seed oil diet that contained more than five times as much linoleic acid. These results show that a certain amount of polyunsaturated fat, as well as a high level of dietary fat, is required to promote mammary carcinogenesis.

Potent tumor-initiating activity of the 3,4-dihydrodiol of 7,12-dimethylbenz(a)anthracene in mouse skin.

Abstract: The abilities of the racemic trans -3,4-, 5,6-, and 8,9-dihydrodiols of 7,12-dimethylbenz( a )anthracene to initiate skin tumors in mice were determined by using a two-stage system of tumorigenesis. The 7,12-dimethylbenz( a )anthracene trans -3,4-dihydrodiol was found to be much more active as a tumor initiator than the parent hydrocarbon. The 7,12-dimethylbenz( a )anthracene trans -5,6- and 8,9-dihydrodiols were essentially inactive as skin tumor initiators. Our results suggest that the 3,4-dihydrodiol of 7,12-dimethylbenz( a )anthracene is a proximal carcinogen and that the “bay region” diol-epoxide may be the ultimate carcinogenic form of DMBA.

Anticarcinogenic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene tumor initiation and its relationship to DNA binding.

Abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) pretreatment inhibits the carcinogenicity of both benzo(a)pyrene (B(a)P) and dimethylbenz(a)anthracene when they are applied as skin tumor initiators in female Sencar mice. TCDD caused a marked decrease in the in vivo covalent binding of dimethylbenz(a)anthracene to DNA and RNA but caused a significant increase in the in vivo binding of B(a)P to DNA with relatively little change in RNA binding. The in vivo binding of B(a)P to DNA in the absence of TCDD pretreatment was accompanied by formation of a major hydrocarbon-deoxyribonucleoside adduct which cochromatographed with 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene bound to the exocyclic amino group of guanine. The increased in vivo binding to DNA following pretreatment with TCDD did not results in the formation of detectable amounts of this adduct but in the formation of other, as yet unidentified, adducts. It is suggested, partly on our observation, that the absence of the adduct of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene bound to guanine corresponded to the marked tumor-inhibitory properties of TCDD and that formation of this adduct may be a critical but by itself an inadequate step in B(a)P-induced mouse skin carcinogenesis. Thus, the inhibition by TCDD of B(a)P skin tumorigenesis correlated with the loss of known hydrocarbon-deoxyribonucleoside adducts but not with the total bindingmore » to DNA. This stresses the importance of the qualitative, not just the quantitative, nature of the hydrocarbon-DNA interactions and its subsequent relationship to carcinogenesis.« less

Systemic two-stage carcinogenesis in the epithelium of the forestomach of mice using 7,12-dimethylbenz(a)anthracene as initiator and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate as promoter.

Abstract: In a modified two-stage carcinogenesis experiment, the effectiveness of the initiator 7,12-dimethylbenz(a)anthracene (DMBA) and the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) in the epithelium of the forestomach of the mouse has been investigated. Fifty mice were treated intragastrically with a single dose of DMBA (50 mg/kg body weight), followed by repeated intragastric administration of TPA (10 mg/kg body weight) over a period of 35 weeks. In comparison with the corresponding control groups (no treatment, DMBA initiation only, and TPA treatment only), the initiated and promoted group clearly showed the highest tumor incidence in the target organ (45 tumor-bearing animals of 50 animals). No tumors of the forestomach were found in the untreated control group and the TPA-treated group, whereas in the DMBA-initiated group, ten animals had developed tumors of the forestomach. In addition to the mouse skin model for two-stage carcinogenesis, the mouse forestomach appears to respond to DMBA initiation-TPA promotion. This organ provides an additional tissue with which to investigate tumor promotion and further to ascertain specific parameters of the promotion step.

Mutagenicity and Tumor-initiating Activity of Fluorinated Derivatives of 7,12-Dimethylbenz(a)anthracene

Abstract: 7,12-Dimethylbenz(a)anthracene (DMBA) and its 1-, 2-, 5-, and 11-fluoro derivatives were tested to determine their mutagenicity for ouabain resistance in Chinese hamster V79 cells and their tumor-initiating activity in mouse skin. Inasmuch as V79 cells do not metabolize polycyclic aromatic hydrocarbons, mutagenesis was tested both in the presence and in the absence of golden hamster embryo cells capable of metabolizing polycyclic aromatic hydrocarbons. Neither DMBA nor any of the fluorinated derivatives showed mutagenicity for V79 cells in the absence of the golden hamster cells. In the presence of these cells, DMBA and 11-fluoro-DMBA exhibited a comparable mutagenic response that was dose dependent. At a dose as low as 0.01 ..mu..m, a 7- to 10-fold increase in the frequency of ouabain-resistant mutants was observed. The other derivatives were either inactive or required more than a 1000-fold higher dose to induce a comparable mutagenic response. Similarly, both DMBA and 11-fluoro-DMBA at 100 nmol initiated tumors in 100% of the tested mice, whereas the other fluorinated derivatives at this dose initiated skin tumors in 15% or less of the treated mice. The average number of papillomas per mouse induced by 1-, 2-, and 5-fluoro-DMBA was more than 100-fold lower than the number inducedmore » by DMBA or 11-fluoro-DMBA. These results suggest that carbon positions 1 and 2 of DMBA, which are located at the bay region, and position 5, which is located at the K-region, are involved in the metabolic activation of DMBA into mutagenic and carcinogenic metabolites.« less

Comparison of Metabolism-mediated Binding to DNA of 7-Hydroxymethyl-12-methylbenz(a)anthracene and 7,12-Dimethylbenz(a)anthracene

Abstract: Comparison of the binding to DNA of 7-hydroxymethyl-12-methylbenz( a )anthracene and 7,12-dimethylbenz( a )anthracene (DMBA) catalyzed by mouse embryo cells in culture or by rat liver microsomes indicates that the products formed are different for the two hydrocarbons Thus, the hydroxy compound is not an intermediate in the binding of DMBA to DNA in these systems Binding of the hydroxy compound to DNA in mouse embryo cells is less efficient than for DMBA and is inhibited by 1,1,1-trichloropropylene 2,3-oxide, an inhibitor of epoxide hydrase This and the fluorescence spectra of the hydroxy compound-DNA adducts indicate that the hydroxy compound is activated for DNA binding through the formation of a diol-epoxide in the 1,2,3,4-ring As previously found for DMBA, this is consistent with the activation of this compound through a bay-region diol-epoxide

Identification of 7,12-dimethylbenz[a]anthracene metabolites that lead to mutagenesis in mammalian cells.

Abstract: The mutagenicity of 7,12-dimethylbenz[a]-anthracene (DMBA) and 11 of its enzymatically derived metabolites was tested with Chinese hamster V79 cells for identification of mutagenic metabolites. The metabolites consisted of 7-hydroxymethyl-12-methylbenz[a]anthracene, 7-methyl-12-hydroxymethylbenz[a]anthracene, 7,12-dihydroxymethylbenz[a]anthracene, three trans-3,4-diols, two trans-5,6-diols, and three trans-8,9-diols, all of which derived from DMBA or from the hydroxymethyl derivatives. Mutations were characterized by resistance to ouabain and 6-thioguanine. None of the tested metabolites were mutagenic in V79 cells, which do not metabolize polycyclic aromatic hydrocarbons. Therefore, mutagenesis in the V79 cells was tested in the presence of golden hamster cells capable of metabolizing polycyclic aromatic hydrocarbons (cell-mediated assay). In this assay, DMBA, 7-hydroxymethyl-12-methylbenz[a]anthracene, 7-methyl-12-hydroxymethylbenz[a]anthracene, and their trans3,4-diols were mutagenic for both genetic markers, and the mutagenic response increased as a function of the hydrocarbon dose. All other metabolites were either inactive or showed up to a 4-fold higher mutation frequency than the untreated V79 cells for ouabain and 6-thioguanine resistance. The DMBA-trans-3,4-diol was the only metabolite that was more active than DMBA itself; at 0.05 μM it was 6-8 times more active than DMBA itself; at 0.05 μM it was 6-8 times more active than DMBA in inducing both ouabain and 6-thioguanine resistance. This diol was mutagenic at a dose as low as 0.01 μM. Mutagenesis by DMBA and the trans-3,4-diols was inhibited by 7,8-benzoflavone, an inhibitor of mixed-function oxidases. Analysis of DMBA metabolism in intact golden hamster cells indicated that DMBA-trans-3,4-diol is one of the major metabolites produced. Our results therefore suggest that DMBA-trans-3,4-diol may be metabolized to a diol-epoxide, presumably the trans-3,4-diol-1,2-epoxide, which may be a major reactive metabolite responsible for DMBA mutagenicity in mammalian cells.

The effects of hyalurodinase upon tumor formation in BALB/c mice painted with 7,12-dimethylbenz-(a)anthracene.

Abstract: Experiments were performed to investigate the effects of hyaluronidase on chemical carcinogenesis. Two experiments were carried out using BALB/c mice. In the first experiment the mice were divided into three groups, viz. (1) painted with 7,12-dimethylbenz(a)anthracene (DMBA), (2) injected with hyaluronidase and painted with DMBA and (3) injected with saline and painted with DMBA. In the second experiment the mice were divided into three groups: (1) painted with DMBA, (2) injected with hyaluronidase and painted with DMBA and (3) injected with heat-inactivated hyaluronidase and painted with DMBA. The tumor incidence and size of tumors were significantly lower in the group treated with hyaluronidase than in the other groups. The latent period was increased. The mitotic index of the skin adjacent to the tumors at the end of the experiment was decreased. These studies show that hyaluronidase can act as an anticarcinogenic agent.

Mammary tumorigenesis in the rat following prenatal exposure to diethylstilbestrol and postnatal treatment with 7,12-dimethylbenz[a]anthracene.

Abstract: Pregnant rats were injected with vehicle or 1.2 μg diethylstilbestrol (DES) during wk 2 or 3 of gestation; their female offspring (∼ 50 d old) were fed 7,12‐dimethyl‐benz[a]anthracene (DMBA). The survivors (27 per group) were sacrificed 30 wk later. The three groups did not differ in the number of tumor‐bearing animals; however, significantly more palpable mammary tumors arose in both DES‐exposed groups than in controls. When DES was given during the second trimester, palpable tumors appeared earlier than in the other two groups. Thus, transplacental exposure to DES potentiated the action of a known carcinogen (DMBA) on rat mammary tissue. These results raise the possibility that, for young women, DES exposure in utero may have affected tissues other than the vagina. Further investigation is warranted, with special emphasis on the effects of DES on mammary and other estrogen‐sensitive tissues.

Inhibition of preovulatory gonadotropin secretion and stimulation of prolactin secretion by 7,12-dimethylbenz(a)anthracene in Sprague-Dawley rats.

Abstract: Serum luteinizing hormone, follicle-stimulating hormone, prolactin, thyroid-stimulating hormone, and growth hormone and hypothalamic luliberin and thyroliberin contents were measured at given times of the estrous cycle in a dimethylbenz( a )anthracene (DMBA)-susceptible strain of rat (Sprague-Dawley) and in a DMBA-resistant strain of rat (Wistar) for periods up to the appearance of the first mammary tumors in DMBA-susceptible animals Tumors usually appeared with ≃100% incidence around the 14th to 15th estrous cycle after DMBA treatment in Sprague-Dawley rats Hormonal determinations were done by using groups of 4-day cycling rats of both strains which were given DMBA or the vehicle (sesame oil) on a single diestrus I at around 55 days of life Animals were sacrificed by decapitation without previous anesthesia on the morning and afternoon of proestrus and estrus during the 5th and 11th estrous cycles after treatment In Sprague-Dawley female rats, DMBA significantly inhibited luteinizing hormone and follicle-stimulating hormone surges and stimulated the prolactin surge on the afternoon of proestrus at any estrous cycle after treatment (the timing of preovulatory surges was the same in both strains for any estrous cycle or treatment); no difference was found for any hormone at other times of the estrous cycle In contrast, Wistar rats did not show deranged preovulatory or basal prolactin and gonadotropin release after treatment with the carcinogen; in addition, no difference was found for any other hormone at any time tested These results show that there is a specific and transient hormonal deregulation in a DMBA-susceptive strain of rats Inasmuch as the hormonal imbalance was essentially the same throughout the induction period, an early and persistent alteration in centers implicated in the hormonal cyclicity of the hypothalamopituitary axis must result from DMBA treatment

The initiation of tumours on mouse skin by dihydrodiols derived from 7,12-dimethylbenz(a)anthracene and 3-methylcholanthrene.

Abstract: The cis-2a,3-diol and the trans-4,5-, trans-7,8-, trans-9,10- and trans-11,12-dihydrodiols of 3-methylcholanthrene and the trans-3,4, trans-5,6-, trans-8,9- and trans-10,11- dihydrodiols of 7,12-dimethylbenz[a]-anthrancene have been tested, in comparison with the parent hydrocarbons, for their abilities to initiate skin tumours in female CDI mice. Groups of mice received a single topical application (25 μg) of a diol or of a hydrocarbon, and 1 week later repeated topical applications (1 μg) of 12–0-tetradecanoyl-phorbol-13-acetate were commenced. The results show that the diols capable of being converted into bay-region vicinal diol-epoxides, i.e. the 9,10-diol of 3-methylcholanthrene and the 3,4-diol of 7,12-dimethylbenz[a]anthrancene were active as initiating agents but that they were no more active than their parent hydrocarbon. The K-region 5,6-diol of 7,12-dimethylbenz[a]anthrancene, which cannot be converted directly into a vicinal diol-epoxide, was also active as a tumour-initiating agent when applied to mouse skin.

Age as a modifying factor of 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in the lewis rat.

Abstract: The influence of age at DMBA administration on (1) susceptibility to mammary tumor development, (2) the proportion of tumors which are ovary-dependent, and (3) the frequency of spontaneous tumor regression was examined in female Lewis rats between 25 and 200 days of age. Tumor development was monitored for a 12-month period after carcinogen administration. Age at carcinogen administration affected (1) the number of tumors induced, (2) the latent period of tumor development, and (3) the number of tumors which regressed spontaneously. More tumors developed in young rats; however, a large fraction of these tumors regressed spontaneously. The frequency of spontaneous tumor regression was strongly age-related, being highest in rats treated up to 70 or after 150 days of age. Mean latent period of development of tumors which regressed spontaneously (SRT) was significantly shorter than that of tumors which grew progressively (PGT). Furthermore, mean latent period of SRT development was significantly shorter in rats treated at 25 or 50 days of age. In contrast, all age-groups were equally susceptible to the development of progressively growing tumors (PGT). PGT incidence, mean latent period of PGT development, mean numbers of PGT per PGT-bearing rat and the relative proportion of PGT which were ovary-dependent were similar for all age-groups at the end of 12 months. These results indicate that, in the Lewis rat strain, age does not confer significant or permanent refractoriness. Furthermore, spontaneous tumor regression is a frequent and strongly age-related phenomenon.

Photodynamic cytotoxicity of mammalian cells exposed to sunlight-simulating near ultraviolet light in the presence of the carcinogen 7,12-dimethylbenz(a)anthracene.

Abstract: — The coal-derived carcinogen 7,12-dimethylbenz(a)anthracene (DMBA), added to cultures of V79 Chinese hamster, C3H mouse 10T1/2, and human HeLa cells, enhances photolethality induced by the sunlight-simulating emission from Westinghouse Sun Lamps (- 29˜100 nm) but only in the presence of O2. Treatment of cells with DMBA after irradiation is without lethal effect; the endoperoxide of DMBA is ineffective both before as well as after irradiation, and DMBA incubation before far-UV exposure (254 nm) is protective. Cells rendered photosensitive by incubation with DMBA rapidly lose their sensitivity (in < 10 min, 37°C) if incubated in a DMBA-free solution containing serum, but maintain their sensitivity at least for several hours if a serum-free solution is used. Although DMBA enhances light-induced killing of cells in all phases of the cycle, those undergoing DNA syntheses are preferentially sensitized. The data support photodynamic lethality due to one or both of the following: (1) the reaction with DNA of either DMBA radicals followed by oxidation, or DMBA-produced singlet oxygen; or (2) the peroxidation of lysosomal membranes followed by the release of hydrolases including DNAses. As a model system of the combined effects of a fossil-fuel derived polycyclic aromatic hydrocarbon and sunlight, the results with DMBA + near-UV are discussed in the context of altered cell properties (e.g. neoplastic transformation) in sublethally affected cells.

Comparison of mutagenesis and malignant transformation by dihydrodiols from benz[a]anthracene and 7,12-dimethylbenz[a]anthracene.

Abstract: Five dihydrodiols derived from benz[a]anthracene (BA) and 4 dihydrodiols derived from 7,12-dimethylbenz[a]anthracene (DMBA) have been tested, together with the parent hydrocarbons, for their abilities to induce mutations to 8-azaguanine resistance in V79 (Chinese hamster cells and malignant transformation in M2 mouse fibroblasts. The syn- and anti-isomers of benz[a]anthracene 8,9-diol 10,11-oxide were also tested for biological activity in these two systems. The non-K-region 1,2- and 3,4-dihydrodiols of BA induced mutations but the non-K-region 8,9-dihydrodiol and the K-region 5,6-dihydrodiol were inactive as mutagens; none of these BA diols transformed M2 mouse fibroblasts. The 3,4- and the 8,9-dihydrodiols derived from 7,12-dimethylbenz[a]anthracene induced mutations in V79 cells and malignant transformation in M2 mouse fibroblasts and both were more active than the hydrocarbon itself. The K-region 5,6-dihydrodiol and the non-K-region 10,11-dihydrodiol of DMBA were inactive in both test systems. The results are not inconsistent with other data suggesting that the metabolic activation of both BA and DMBA occurs through conversion of the respective 3,4-dihydrodiols into the related vicinal diol-epoxides, although other dihydrodiols may also be involved in vivo. Both the BA diol-epoxides tested were mutagenic, but although the anti-isomer transformed M2 fibroblasts, the syn-isomer was inactive.

Modification of the effect of a gonadoliberin analog on 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors by hormone replacement.

Abstract: A gonadoliberin analog, (d-leucyl 6 , desglycyl-NH 2 10 , prolyl ethylamide 9 ) gonadoliberin, is known to suppress ovarian function and plasma prolactin levels. Its antitumor activity was evaluated against mammary tumors induced in Sprague-Dawley rats by dimethylbenz(a)anthracene. Observations were made when the analog, referred to as A-43818, was given alone and together with estrogen replacement or perphenazine. A-43818, 10 µg s.c. twice a day for 6 weeks, was highly effective in producing tumor remissions. All of the 11 animals survived throughout the observation period, complete regressions occurred in 8 of 13 tumors, and 2 were classified as static. None of the 16 tumors in 12 control rats regressed, and there were 4 deaths. When estradiol benzoate, 2 µg s.c. each day, was administered with the A-43818, antitumor activity was suppressed; only 2 of 17 tumors regressed, 6 were static, and 5 of the 10 rats in this group died. Perphenazine, 1 mg i.m. daily, a dose known to cause hyperprolactinemia, also impaired the efficacy of A-43818. Three of 14 tumors regressed, 6 were static, and the rest continued to grow; 3 of the 12 rats died within 6 weeks of starting treatment.

Biochemical basis for cytotoxicity of 7,12-dimethylbenz(a)anthracene in rat liver epithelial cells.

Abstract: When the effects of 7,12-dimethylbenz(a)anthracene (DMBA) on normal and malignant rat liver epithelial cells were compared in a colony inhibition assay, this carcinogen showed a preferential cytotoxic action on the normal cells. In investigations of the biochemical basis of this selective toxicity, it was found that both cell lines were similarly effective in binding DMBA to DNA and that both cell lines had the capacity to metabolize this carcinogen. However, the hepatoma cells were more efficient than were the normal cells in generating very polar metabolites (not organic solvent extractable). These studies suggest that the basis of the resistance of the hepatoma cells to the toxicity induced by DMBA lies in their ability to detoxify biologically active metabolites. Several phenols were examined as possible toxic metabolites of DMBA, but these were not toxic at dose levels at which DMBA kills most of the normal cells.

Synthesis of trans-3,4-dihydroxy-3,4-dihydro-7,12-dimethylbenz[a]anthracene, a highly carcinogenic metabolite of 7,12-dimethylbenz[a]anthracene

Abstract: Das Benzanthracen (I) wird in die isomeren Hydroxyderivate (II) ubergefuhrt, deren Oxidation nach Swern die isomeren Ketone (IIIa) und (IIIb) liefert, die chromatographisch getrennt werden.

Estrogenic properties of 3,9-dihydroxy-7,12-dimethylbenz[a]anthracene in rats.

Abstract: Previously, the 3,9-dihydroxy derivative of benz[a]-anthracene was shown to be weakly estrogenic. The availability of the related diol of the mammary carcinogen dimethylbenz[a]-anthracene, i.e., 3,9-dihydroxy-7,12-dimethylbenz[a]anthracene (3,9-diOHDMBA), prompted a similar study of its estrogenic properties. The competitive binding studies of 3,9-diOHDMBA with 17beta-estradiol in the uterine cytosol of immature SD rats gave a Ka of 1.7 x 10(8) M-1. 17beta-Estradiol (10(-9) M) binding to the 8S binding protein was inhibited by 3,9-diOHDMBA at concentrations similar to those of nafoxidine HCl (1 x 10(-5) M). Bioassay demonstrated that the diol possesses 1/4,464 the activity of 17beta-estradiol.

Quantitative assessment of generalized epithelial changes in tracheal mucosa following exposure to 7,12-dimethylbenz(a)anthracene.

Abstract: Sequential morphological changes occurring after brief carcinogen exposures of heterotopic tracheal transplants in rats were semiquantitatively studied. Tracheas were exposed to 7,12-dimethylbenz( a )anthracene for 1, 2, or 4 weeks, during which time means of 138, 152, and 160 µg 7,12-dimethylbenz( a )anthracene, respectively, were delivered. The first two types of exposures resulted only in generalized epithelial changes; these included hyperplasia and early metaplasia, both of which regressed rapidly, and persistent atrophic alterations. No focal epithelial lesions or tumors developed. The third type of exposure (160 µg 7,12-dimethylbenz( a )anthracene delivered in 4 weeks) resulted in the appearance of generalized mucosal changes with long-lasting, severe inhibition of mucus production. In addition, focal metaplastic lesions reappeared at 4 to 8 months after exposure, and invasive carcinomas developed after 1 year with an incidence of 9%. Overall carcinoma incidence, including carcinoma in situ , was 15%. The studies emphasize the importance of the duration of carcinogen exposure, and they demonstrate the emergence of focal lesions when effective carcinogenic exposures are being used. The possible significance of epithelial atrophy in the pathogenesis of cancer in this experimental model is discussed.

Effects of Low-Level X-Radiation on 7,12-Dimethylbenz[a]anthracene-Induced Lingual Tumors in Syrian Golden Hamsters

Abstract: The effects of repeated low-dose-rate, high-dose-rate x radiation of the head and neck on lingual tumor induction by 7,12-dimethylbenz(a)anthracene (DMBA) in Syrian golden hamsters were studied. Animals received either topical application of 0.5% DMBA in acetone on the lateral middle third of the tongue three times a week for 15 consecutive weeks, 20-R x-radiation exposures of the head and neck once a week for 15 consecutive weeks, or concurrent radiation and DMBA treatments for 15 consecutive weeks. Animals were examined visually at regular intervals, and all were killed 35 weeks after the start of treatments. All tissues were then examined histopathologically. Animals receiving radiation alone had no detectable changes. Animals receiving DMBA plus radiation had an excess of papillomas compared to animals receiving only DMBA (35% vs. 15%). In addition, an excess of nonlingual oral tumors (lip, gingiva, and floor of mouth) was found in DMBA-treated plus radiation-treated animals versus DMBA-treated animals. These results suggest that repeated, localized, low-level x-radiation exposures enhance chemical tumorigenesis in a variety of oral tissues of Syrian golden hamsters.

Mechanism of Ovarian Carcinogenesis: Effect of 7,12-Dimethylbenz[a]anthracene Administration on Intrasplenic Ovarian Grafts in Unilaterally Ovariectomized C3HeB/Fe Mice

Abstract: A single oral administration of 7,12-dimethylbenz[a]anthracene (DMBA) 2 weeks after intrasplenic grafting of ovarian tissue in unilaterally ovariectomized C3HeB/Fe mice resulted in a high tumor incidence (47%) in the grafted tissue, with only 1 tumor (3%) in the orthotopic ovary. No tumors were seen in the control group (unilaterally ovariectomized mice given intrasplenic grafts of ovarian tissue without subsequent DMBA administration), nor did tumors develop in response to DMBA treatment in mice with both ovaries in situ and no grafted tissue in the spleen. The results indicated that some local change caused by the grafting procedure rendered the tissues more sensitive to the action of DMBA and/or more responsive to gonadotropic stimulation.