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Showing papers on "7,12-Dimethylbenz[a]anthracene published in 1973"


Journal ArticleDOI
TL;DR: The “K-region” epoxide of 7-hydroxymethyl-12-methylbenz[a] anthracene did not induce adrenal necrosis when tested in Sprague-Dawley rats, and the epoxide metabolites were found to react with polyguanylic acid.

54 citations


Journal ArticleDOI
TL;DR: In the alkylation of 4-(p-nitrobenzyl)pyridine, 7,12-dimethyl-benz[a]anthracene 5, 6-oxide was more active than the 5,6-oxides of 7-methylbenZ[a]-anthracenes and benz[a], and the GSH conjugates were more stable to acid than conjugate derived from other arene oxides.
Abstract: The syntheses of 7,12-dimethylbenz[ a ]anthracene 5,6-oxide, 7-acetoxymethyl-12-methylbenz[ a ]anthracene 5,6-oxide and a product that appears to be mainly 7-hydroxymethyl-12-methylbenz[ a ]anthracene 5,6-oxide are described. The compounds readily rearranged to phenols in the presence of mineral acid, and 7,12-dimethylbenz[ a ]anthracene 5,6-oxide and its 7-hydroxymethyl derivative reacted slowly with water to yield trans -5,6-dihydro-5,6-dihydroxy-7,12-dimethylbenz[ a ] anthracene and trans -5,6-dihydro-5,6-dihydroxy-7-hydroxymethyl-12-methylbenz [ a ]anthracene respectively. Both epoxides were converted enzymically by rat liver microsomal fractions and homogenates into the related trans -dihydrodiols. The epoxides reacted chemically with GSH to form conjugates that were identical with the conjugates formed when the epoxides were incubated with rat liver homogenates. The GSH conjugates were more stable to acid than conjugates derived from other arene oxides. In the alkylation of 4-( p -nitrobenzyl)pyridine, 7,12-dimethyl-benz[ a ]anthracene 5,6-oxide was more active than the 5,6-oxides of 7-methylbenz[ a ]-anthracene and benz[ a ]anthracene.

38 citations


Journal ArticleDOI
TL;DR: The slower-moving region of radioactivity may contain a mixture of conjugates since the dihydrodiols that are formed during the metabolism of 7,12-dimethylbenz[a]anthracene by rat-liver homogenates are all converted by further metabolism into water-soluble derivatives that are located in this region of the chromatograms.

34 citations


Journal Article
TL;DR: Estradiol benzoate- and testosterone propionate-treated rats exhibited fewer developing ovarian follicles and no corpora lutea, and progesterone treatment was without effect on the mammary fibroadenoma response to DMBA and ovarian structure.
Abstract: Female Sprague-Dawley 5-day-old rats were given s.c. either 0.05 ml sesame oil, 1.25 mg progesterone, 0.1 mg estradiol benzoate, or 1.25 mg testosterone propionate. At 55 days of age all rats were given 20 mg of 7,12-dimethylbenz(a)anthracene (DMBA) by stomach tube. All rats were killed at 190 days of age. Both the estradiol and the testosterone propionate treatments decreased the mammary adenocarcinoma response to DMBA and increased the mammary fibroadenoma response to DMBA. Both estradiol benzoate- and testosterone propionate-treated rats exhibited fewer developing ovarian follicles and no corpora lutea. Only testosterone propionate-treated rats exhibited fewer developing ovarian follicles and no corpora lutea. Only testosterone propionate-treated rats exhibited lactation. Progesterone treatment increased the mammary adenocarcinoma response to DMBA and was without effect on the mammary fibroadenoma response to DMBA and ovarian structure.

34 citations


Journal ArticleDOI
TL;DR: In contrast, when progesterone injections were begun 2 days after feeding DMBA, there was a trend towards enhancement of tumour yield, and continuous hormone administration appeared more effective than shorter treatment regimens.
Abstract: Effects of Time and Duration of Progesterone Administration on Mammary Tumours Induced by 7,12-Dimethylbenz(a)Anthracene in Sprague-Dawley Rats

33 citations


Journal Article
TL;DR: The data illustrate, for the first time, the ability of the mammary tissue to metabolize 7,12-dimethylbenz(a)anthracene.
Abstract: The metabolism of 7,12-dimethylbenz(a)anthracene to hydroxymethyl derivatives differs in hepatic and mammary tissue homogenates. Countercurrent distribution and carrier recrystallization have been shown to be effective additional tools in the identification of 7-hydroxymethyl-12-methylbenz(a)anthracene, 12-hydroxymethyl-7-methylbenz(a)anthracene, and 7,12-dihydroxymethylbenz(a)anthracene. In the hepatic tissue, 7,12-dimethylbenz(a)anthracene is transformed into all three of these metabolites whereas the mammary gland formed only the monohydroxy compounds. Pretreatment of rats with 3-methylcholanthrene induces a marked increase in 7,12-dimethylbenz(a)anthracene-metabolizing enzymes in the liver causing further conversion of the 7-hydroxymethyl-12-methylbenz(a)anthracene, 12-hydroxymethyl-7-methylbenz(a)anthracene, and 7,12-dihydroxy-7,12-dimethylbenz(a)anthracene to more polar components. In contrast, mammary gland caused a diminution but still detectable level of the carcinogenic 7-hydroxymethyl-12-methylbenz(a)anthracene and a noticeable increase in the conversion to 12-hydroxymethyl-7-methylbenz(a)anthracene. The data illustrate, for the first time, the ability of the mammary tissue to metabolize 7,12-dimethylbenz(a)anthracene.

24 citations


Journal Article
TL;DR: The cell-mediated immune response against tumor-associated antigens of s.c. fibrosarcomas induced by 7,12-dimethylbenz( a )anthracene in BALB/c mice was studied by an in vitro microtest based on 51Cr release.
Abstract: The cell-mediated immune response against tumor-associated antigens of s.c. fibrosarcomas induced by 7,12-dimethylbenz( a )anthracene in BALB/c mice was studied by an in vitro microtest based on 51Cr release. Eight tumors were tested at the first, fifth, and ninth transplant generation with spleen lymphocytes from BALB/c mice that were immunized against syngeneic tumors, allogeneic tumors, or embryo cells. Individual antigens were detected on fibrosarcomas at the first and fifth transplant passage, whereas they were undetectable on the eight tumors tested at the ninth passage. Lymphocytes sensitized against a pool of five C3Hf fibrosarcomas induced by 7,12-dimethylbenz( a )anthracene revealed cross-reacting antigens in one, seven, and eight out of the eight BALB/c fibrosarcomas tested at the first, fifth, and ninth transplants, respectively. Similarly, lymphocytes sensitized against embryo cells were cytotoxic on two fibrosarcomas out of the six tested at either the first or fifth passage and on six out of the seven tumors tested at the ningh passage.

18 citations


Journal ArticleDOI
TL;DR: The morphological changes observed in the endocrine glands, genital tracts and non-neoplastic mammary tissue, considered in relation to previously reported data, suggest that hypothyroidism reduced the tumour yield mainly by secondarily inhibiting somatotrophin production and secretion, although the effect of decreased food intake could not be excluded completely.
Abstract: Hypothyroidism, alone or combined with progesterone, significantly decreased 7,12-dimethylbenz(a)anthracene (DMBA) mammary tumorigenesis relative to controls. However, the decrease was less in the progesterone-treated group, and statistical analysis showed that progesterone enhanced tumorigenesis to the same extent in hypothyroid animals as in the controls. Most tumours in hypothyroid progesterone-treated rats were adenocarcinomata; in the absence of the hormone most tumours were benign. However, the difference between the tumour types in the 2 groups was not statistically significant. The morphological changes observed in the endocrine glands, genital tracts and non-neoplastic mammary tissue, considered in relation to previously reported data, suggest that hypothyroidism reduced the tumour yield mainly by secondarily inhibiting somatotrophin production and secretion, although the effect of decreased food intake could not be excluded completely. The higher tumour yield in the hypothyroid progesterone-treated rats may have been due to higher circulating levels of prolactin in this group compared with those in the hypothyroid group which received no hormone.

16 citations


Journal ArticleDOI
TL;DR: The sensitivity of feeding tests in detecting the carcinogenic properties of a small dose of 7,12-dimethylbenz[ a ]anthracene in female rats was increased when the compound was given to rats at an earlier age and when a high-fat diet containing 1% polyoxyethylene monostearate was administered.

16 citations




Journal ArticleDOI
TL;DR: With repeated intravenous administrations of DMBA transplantable myeloid rat leukaemia has been induced, 2 forms have developed: the subacute form maintained with and the main form, which is currently being treated with chemotherapy.
Abstract: With repeated intravenous administrations of DMBA transplantable myeloid rat leukaemia has been induced. In the course of transplantations 2 forms have developed: (1) the subacute form maintained with

Journal ArticleDOI
TL;DR: The results indicate that the pattern observed for the regressing tumour is similar to that observed for normal hormone-dependent tissue undergoing physiological changes.



Journal ArticleDOI
TL;DR: The permanent reduction in CFUs after neonatal irradiation contrasted sharply with the short-term effect of such a dose administered to adult animals, and the effect of DMBA on the number of bone marrow stem cells was not merely quantitative: the CFUs remaining after treatment had a diminished ability to form spleen colonies on secondary transplantation.
Abstract: Treatment of neonatal inbred CFW/D mice with 7, 12- dimethylbenzSTAa!anthracene (DMBA) or gamma -irradiation suppressed the number of colony-forming units (CFUs) or stem cells in the bone marrow. At 14 days after administration, DMBA (30 mu g) had induced an 85% depression; at 60 days post treatment, there was still a 60 to 70% suppression. The extent and duration of the depression after the neonatal exposure to 400 rads (whole body) were similar. The permanent reduction in CFUs after neonatal irradiation contrasted sharply with the short-term effect of such a dose administered to adult animals. For both DMBA and irradiation treatment, the extent of the depression was dose dependent at low doses only. The effect of DMBA on the number of bone marrow stem cells was not merely quantitative: The CFUs remaining after treatment had a diminished ability to form spleen colonies on secondary transplantation. (auth)

Journal ArticleDOI
TL;DR: DMBA ( 7,12 -dimethylbenz[a]anthracene)-coated threads were placed in the vaginal fornix of 4–5 week-old ICR mice and a wide range of karyotypic composition was revealed, including a heterogeneous cell population with a majority of the metaphase plates containing four metacentric chromosomes.

Journal ArticleDOI
01 Jan 1973-Oncology
TL;DR: Chronic forced feeding of iodine in small doses accelerates mammary tumour appearance in female rats after treatment with 7,12-dimethylbenz-(a)anthracene; extended exposure to cold, which also results.
Abstract: Chronic forced feeding of iodine in small doses accelerates mammary tumour appearance in female rats after treatment with 7,12-dimethylbenz-(a)anthracene; extended exposure to cold, which also results


Journal ArticleDOI
TL;DR: In vitro Experimente mit isolierten Kalbsuteruskernen in Tris-EDTA-Puffer Losungen oder Uterus Cytosol zeigten, das sowohl Oestradiol-17β (E2) wie 7,12-Dimethylbenz(a)antracen (DMBA) in den Kern transportiert wird as discussed by the authors.
Abstract: In vitro Experimente mit isolierten Kalbsuteruskernen in Tris-EDTA-Puffer Losungen oder Uterus Cytosol zeigten, das sowohl Oestradiol-17β (E2) wie 7,12-Dimethylbenz(a)antracen (DMBA) in den Kern transportiert wird. Eine spezifische Bindung an Kernreceptoren konnte dabei nicht festgestellt werden. Weiterhin untersuchten wir den gegenseitigen Einflus von DMBA auf den Transport vonE2 in den Kern. Dabei fand sich kein Einflus auf den Transport oder auf die Menge der transportierten Substanzen.



Dissertation
01 Jan 1973
TL;DR: To test the theory that a thymus-dependent immunological surveillance mechanism is important in tumor prevention, nude mice and their phenotypically normal littermates were treated with 7, 12-dimethylbenz(a)anthracene and then croton oil as a promoter; only one of 21 Nu mice developed a tumor.
Abstract: Considerable evidence supports the theory that a thymus-dependent immunological surveillance mechanism is important in tumor prevention. To this end we expected the congenitally athymic (nude) mouse to have many spontaneous tumors. We have not observed spontaneous tumors in the nude mice in our colony. Because the nude mice have a short lifespan, we thought that maybe the mice died before spontaneous tumors had time to develop. Therefore, we attempted to induce tumors in nude mice and their phenotypically normal littermates with the carcinogen 7, 12-dimethylbenz(a) anthracene. In every experiment each normal littermate developed papillomas and none of the nudes developed a papilloma. We do not believe this result was due to the hairless condition of the nude mice as we successively induced papillomas with the same carcinogen in the hairless (hr/hr) mutant. We then considered that some thymic influence might be required for the production of some types of tumors. To test this idea, nude mice (NU), nudes implanted with thymus glands (Nu-tg), nudes injected with thymus cells (Nu-tu), and phenotypically normal littermates (NLM) were treated with 7, 12-dimethylbenz(a)anthracene and then croton oil as a promoter. All of the NLM, Nu-tg, and Nu-tc developed tumors; only one of 21 Nu mice developed a tumor. Statement of Permission to Copy In presenting this thesis in .-partial fulfillment of the requirements for an advanced degree at Montana State Univer­ sity, I agree that the library shall make it freely available for inspection. I further agree that permission for exten­ sive copying of this thesis for scholarly purposes may be . granted by my major professor, or, in his absence, by the Director of Libraries. It is understood that any copying dr publication of this, thesis for financial gain shall not be allowed without my written permission. S ig n a tu r e i& 0 5 r % _

Journal ArticleDOI
01 Jan 1973-Tumori
TL;DR: It was found that either chronic administration of ALS or treatment of very young mice with the serum, greatly reduced the mean survival time of mice, markedly increased the number of tumor bearing mice and the incidence of all histological types of tumors, and decreased their latency period.
Abstract: The present paper describes the effects of repeated administration of rabbit anti-mouse lymphocyte serum (ALS) or normal rabbit serum (NRS) on tumors induced in Charles–River mice by 7,12-dimethylbenz (a) anthracene (DMBA) given at birth. ALS or NRS were given at the same time of DMBA administration and subsequently at weekly intervals for the first 10 weeks of life or at daily intervals for 7 days during the first, second, third or fourth week of life. Incidence, latency, diffusion and histology of the tumors were studied. It was found that either chronic administration of ALS or treatment of very young mice with the serum, greatly reduced the mean survival time of mice, markedly increased the number of tumor bearing mice and the incidence of all histological types of tumors, and decreased their latency period. Administration of ALS in the other experimental groups gave results essentially similar to those observed in DMBA control and NRS treated mice.