Link between Carcinogenicity and Hepatic Metabolism of 7,12-Dimethylbenz(α)anthracene

Feuer, G.; Kellen, J

doi:10.1159/000224994

Cited by 12 publications

(11 citation statements)

References 21 publications

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“…The protective action of coumarin showed a dose-response relationship (table I). These findings agree with our earlier results [11,12], In four different studies extended over 3 years, using two different strains (Sprague-Dawley and Wistar albino rats) and a wide range of coumarin levels, a suppression of cancer was ob served without any apparent toxic side effects. No marked difference was found in the histologic structure of mammary tumors between untreated and coumarin-treated rats, it seems, therefore, that while coumarin reduced the incidence and yield of breast tumors and retarded their formation, it failed to influence the degree of anaplasia once the neoplasm had developed.…”

Section: Discussionsupporting

confidence: 93%

“…Parallel with the reduction of tumor incidence, coumarin brought about an inhibition of hepatic drug metabolism and an increase of serum prolactin (table II). The inhibitory action on DMBA-metabolism by coumarin was concordant with our previous report [11] and is similar to the protection provided by pregnancy against DMBA tumorigenesis [12]. It was an unexpected finding that the administration of coumarin increased serum prolactin.…”

Section: Discussionsupporting

confidence: 91%

“…Previous results from our laboratory indicated that pretreat ment of rats with coumarin significantly reduced the incidence of breast carcinomas induced by DMBA injections [11]. The protection against this compound was associated with a decrease in the ability of the hepatocyte to metabolize the drug [12], Since coumarin elicited no significant hepatic im pairment, the suppression of carcinogenesis in animal experi ments seemed to provide a scope for further investigations into the mechanism of action of the carcinogen. In the present studies, attempts have been made to clarify whether or not the protection provided by coumarin in mammary tumor induc tion can be correlated with blood prolactin levels and whether or not coumarin inhibits hemopoietic and adrenocortical in jury brought about by DMBA.…”

Section: Introductionmentioning

confidence: 95%

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Suppression of 7,12-Dimethylbenz(α) Anthracene-Induced Breast Carcinoma by Coumarin in the Rat

Feuer¹,

Kellen²,

Kovacs³

1976

Oncology

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The effect of oral administration of coumarin on the induction of breast tumors brought about by DMBA has been studied in female Wistar rats. Coumarin given before DMBA caused a significant dose-related suppression of the incidence of adenocarcinomas, although no histologic difference was found in the tumor between untreated and coumarin-treated rats. The growth rate, size and multiplicity were also reduced and tumor occurrence was delayed. Parallel with the suppression, hepatic drug metabolizing activity was decreased and serum prolactin level increased. Coumarin given after DMBA elicited no effect on the carcinogenic potency of DMBA. In contrast to the action on mammary tumorigenesis, coumarin provided no protection against hemopoietic and adrenocortical necrosis brought about by DMBA.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 95%

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Suppression of 7,12-Dimethylbenz(α) Anthracene-Induced Breast Carcinoma by Coumarin in the Rat

Feuer¹,

Kellen²,

Kovacs³

1976

Oncology

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“…Naturally occurring coumarins (NOCs), (e.g. 3 and 8) induce mouse skin tumor initiation in a well-established model of multistage carcinogenesis [32][33][34][35][36].…”

Section: Introductionmentioning

confidence: 99%

A Review of Coumarin Derivatives in Pharmacotherapy of Breast Cancer

Musa

Cooperwood²,

Khan³

2008

CMC

490

190

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The coumarin (benzopyran-2-one, or chromen-2-one) ring system, present in natural products (such as the anticoagulant warfarin) that display interesting pharmacological properties, has intrigued chemists and medicinal chemists for decades to explore the natural coumarins or synthetic analogs for their applicability as drugs. Many molecules based on the coumarin ring system have been synthesized utilizing innovative synthetic techniques. The diversity oriented synthetic routes have led to interesting derivatives including the furanocoumarins, pyranocoumarins, and coumarin sulfamates (COUMATES), which have been found to be useful in photochemotherapy, antitumor and anti-HIV therapy, and as stimulants for central nervous system, antibacterials, anti-inflammatory, anti-coagulants, and dyes. Of particular interest in breast cancer chemotherapy, some coumarins and their active metabolite 7-hydroxycoumarin analogs have shown sulfatase and aromatase inhibitory activities. Coumarin based selective estrogen receptor modulators (SERMs) and coumarin-estrogen conjugates have also been described as potential antibreast cancer agents. Since breast cancer is the second leading cause of death in American women behind lung cancer, there is a strong impetus to identify potential new drug treatments for breast cancer. Therefore, the objective of this review is to focus on important coumarin analogs with antibreast cancer activities, highlight their mechanisms of action and structure-activity relationships on selected receptors in breast tissues, and the different methods that have been applied in the construction of these pharmacologically important coumarin analogs.

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“…However, as the level of DMBA in the plasma was not determined, Dao's (1971) hypothesis cannot be ruled out. Feuer & Kellen (1974b) have also suggested that progesterone exerts its effect on DMBA carcinogenesis through its action on the liver. They found that induction of pregnancy (a progestational state) before DMBA administration significantly reduced the mammary tumour incidence.…”

Section: D)iscussionmentioning

confidence: 99%

Effects of progesterone on mammary carcinogenesis by DMBA applied directly to rat mammae

Jabara¹,

Marks²,

Summers³

et al. 1979

Br J Cancer

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Summary.-The effects and site(s) of action of progesterone on DMBA mammary carcinogenesis in the rat, when a small dose of the carcinogen was applied directly to the inguinal mammary gland, were investigated.No reduction in tumour yield was apparent when progesterone was administered s.c. for 18 days before dusting DMBA. This finding contrasts with a previously reported inhibitory effect on carcinogenesis when hormone treatment was followed by intragastric administration of DMBA.When progesterone injections were begun either 2 days before or 2 days after direct application of DMBA, and were continued until the end of the experiment (135 or 195 days) an enhancement in carcinogenesis was observed similar to that previously demonstrated after gastric intubation of DMBA.These findings, together with previously reported observations, suggest that progesterone may exert its inhibitory effect on carcinogenesis by acting at a site outside the breast, perhaps on the liver. However, it is likely that the hormone acts directly on the mammary tissue to exert its enhancing effect on tumorigenesis.

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Link between Carcinogenicity and Hepatic Metabolism of 7,12-Dimethylbenz(α)anthracene

Cited by 12 publications

References 21 publications

Suppression of 7,12-Dimethylbenz(α) Anthracene-Induced Breast Carcinoma by Coumarin in the Rat

Suppression of 7,12-Dimethylbenz(α) Anthracene-Induced Breast Carcinoma by Coumarin in the Rat

A Review of Coumarin Derivatives in Pharmacotherapy of Breast Cancer

Effects of progesterone on mammary carcinogenesis by DMBA applied directly to rat mammae

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