Biomedical subjects

K Imaida

Publications and source records attributed to K Imaida.

At least 37 records · Page 2Linked to original sources

PubMed2000

Lobe specific effects of testosterone and estrogen on 3,2'-dimethyl-4-aminobiphenyl-induced rat prostate carcinogenesis.

We have previously shown that chronic administration of a pharmacological dose of testosterone propionate (TP) after treatment with the carcinogen, 3,2'-dimethyl-4-aminobiphenyl (DMAB), results in development of invasive and metastatic adenocarcinomas arising from the dorso-lateral and anterior prostate, as well as the seminal vesicles. Co-administration of ethinyl estradiol (EE) with TP increased the yield of carcinomas in the lateral and anterior lobes. In the present experiment, male F344 rats were treated with DMAB for 20 weeks and then co-administered a pharmacological dose of TP together with various doses of EE for 40 weeks. Without hormone(s) administration, carcinomas were confined to the ventral prostate and all were of intra-acinar type. TP administration suppressed development of the ventral prostate carcinomas but caused invasive carcinomas of the lateral and anterior lobes and of seminal vesicles and intra-acinar carcinomas in the dorsal prostate. The appearance of carcinomas in the lateral and anterior prostate was increased by co-administration of EE in a dose-related fashion but carcinomas of the seminal vesicles were inversely reduced. The suppressive influence of TP on ventral carcinoma development was overcome by only the highest dose of EE. It is concluded that estrogen can modify the enhancing effects of TP on induction of rat prostate and seminal vesicle carcinomas in a dose-related fashion with lobe specificity.

Aminobiphenyl Compounds↗

PubMed2000

Delay of DNA-adduct repair and severe toxicity in xeroderma pigmentosum group A gene (XPA) deficient mice treated with 2-amino-1-methyl-6-phenyl-imidazo [4,5-b] pyridine (PhIP).

Group-A xeroderma pigmentosum (XPA) gene-deficient mice are defective in nucleotide-excision repair and highly susceptible to ultraviolet-B-, and 9,10-dimethyl-1,2-benz[a]anthracene (DMBA)-induced skin carcinogenesis. In this study, changes of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP)-DNA adduct formations in the liver, colon and lung, as assessed by the 32P-postlabeling method and immunohistochemical analysis, and carcinogenic and/or toxic susceptibility of both sexes of XPA-deficient mice (XPA-/-) to PhIP, which is a carcinogenic heterocyclic amine, was examined. Levels of PhIP-DNA adduct formations in the liver, colon and lung, were almost twice as high in XPA-/- as in wild type mice (XPA+/+) mice, 7 days after a single i.g. administration of PhIP, and their delay in recovery was observed in XPA-/- mice. For the long-term experiment, XPA-/- and XPA+/+ type mice were treated with 80 ppm PhIP in the diet for the first 4 weeks followed by 40 ppm after a 2-week recovery period (long-term experiment I), or 40 ppm PhIP throughout the experiment (long-term experiment II). Severe toxicity, as evidenced by body weight retardation and poor survival, was observed in the PhIP treated XPA-/- mice of both sexes, but not in the XPA+/+. At week 40 the experiments were terminated and histopathological examinations were performed after complete autopsy. Only lymphomas/leukemias were observed as neoplastic lesions, but no significant differences were observed between the groups. As non-neoplastic lesions, degenerating changes, for example in the pancreatic acinar cells, were observed with XPA-/- mice tending to be more sensitive than XPA+/+ mice. The present study demonstrated that PhIP-DNA adduct formations in the liver, colon and lung of XPA-/- mice were demonstrated and their recovery rate was more delayed than XPA+/+ mice, and furthermore, more severe toxicity to PhIP in XPA-deficient mice was observed, but they were not susceptible to PhIP carcinogenicity under the conditions of the experiment.

Animals↗

PubMed2000

Early detection of carcinogenic substances and modifiers in rats.

Over the past 20 years, we have been developing in vivo medium-term bioassay systems in rats for detecting carcinogenic and modifying effects of test compounds. The systems are based on the two-step hypothesis of carcinogenesis. In a liver model, male F344 rats are initially given a single dose of diethylnitrosamine (DEN, 200 mg/kg, i.p.) and starting 2 weeks later are treated with test compounds for 6 weeks and then killed, all rats being subjected to two-thirds partial hepatectomy at week 3. Carcinogenic potential is scored by comparing the numbers and areas per cm(2) of induced glutathione S-transferase placental form (GST-P) positive foci in the livers of groups of about 15 rats with those of corresponding control groups given DEN alone. A positive response is defined as a significant increase in the quantitative values of GST-P-positive foci, such a negative response as no change or a decrease. The results obtained have been compared with reported Salmonella/microsome and long-term carcinogenicity test findings for the same compounds. Of the liver carcinogens, 30 out of 31 (97%) mutagenic and 29 out of 33 (88%) non-mutagenic compounds gave positive results. Carcinogens other than hepatocarcinogens gave a lower proportion of positive results (9 out of 42, 21%). This bioassay also provides information concerning inhibitory potential. The practical utility and benefits of a multi-organ medium-term experimental protocol for early detection of carcinogenic agents and modifiers acting at sites other than the liver are also discussed.

Animals↗

PubMed2000

Experimental prostate carcinogenesis - rodent models.

A number of rodent models of prostate carcinoma development have been established to study mechanisms and modifying potential. All except for transgenic mouse models need long experimental periods for generation of a high yield of cancers. Spontaneous prostate tumor models, while not practical in terms of time and tumor incidences, allow the natural course of multistep neoplasia to be followed without a need for chemical exposure. Carcinogens, especially in combination with testosterone, can induce prostate carcinomas in rats, but none are prostate-specific, so that tumor development in other organs is a complicating factor. Induction of invasive prostate carcinomas in the rat frequently requires long-term administration of a pharmacological dose of testosterone with or without application of a chemical carcinogen. While there are several transgenic mouse models, each also has strong and weak points, and it is therefore necessary to select the best model for the purpose of any experimental study.

Aminobiphenyl Compounds↗

PubMed2000

[Endocrine disrupting chemicals and carcinogenesis--breast, testis and prostate cancer].

Since exogenous hormones, including hormonal medicines such as diethylstilbestrol (DES), have been shown carcinogenic potentials in human and animals, it has been worried about whether endocrine disrupting chemicals(EDCs) have also carcinogenic potentials at their target organs, such as prostate, mammary gland, testes, uterus, ovary, thyroid, etc. In experimental animals, mammary tumors are induced by some pesticides, such as DDT and atrazine. Although testicular tumors are also induced by some EDCs, such as DES and E2, most of tumors are interstitial cell tumors, but not germ cell tumors, which are most common testicular tumors in man. Epidemiological studies showed that there is no EDC which clearly possess carcinogenic potentials in man, except dioxin and hormonal medicines.

Animals↗

PubMed1999

Dose-dependent induction of carcinomas and glutathione S-transferase placental form negative eosinophilic foci in the rat liver by di(2-ethylhexyl)phthalate after diethylnitrosamine initiation.

The dose-dependence of di(2-ethylhexyl)phthalate (DEHP) hepatocarcinogenicity was investigated in male F344 rats which were initially injected with diethylnitrosamine (200 mg/kg, i.p.) and subjected to partial hepatectomy at week 3. The animals were administered DEHP in the diet at concentrations of 30, 300, 3,000, or 12,000 ppm starting 2 weeks after the DEN injection for up to 46 weeks and killed at weeks 8, 24, 48 and 52. Additional groups were given clofibrate (3,000 ppm in diet) or basal diet instead of the DEHP diet. Incidences of hepatocellular carcinomas were 75% (9/12, P < 0.01) for 12,000 ppm, 10% (1/10) for 3,000 ppm, 7% (1/14) for 300 ppm, 0% (0/13) for 30 ppm, 15% (2/13) for clofibrate, and 8% (1/13) for the basal diet group at week 52, 4 weeks after cessation of chemical feeding. Development of glutathione S-transferase placental form (GST-P) positive foci was only slightly increased by clofibrate-administration at week 52 and consistently lower than the control level in the DEHP-treated groups after 24 weeks. In contrast, GST-P negative eosinophilic foci were dose-dependently increased in the more than 300 ppm DEHP and clofibrate treated groups. At the 30 ppm dose level, however, no morphological changes were apparent in the liver. Thus, the non-observed effect level regarding the promotional activity of hepatocarcinogenesis was demonstrated at 30 ppm, the effects being predictable on the basis of development of GST-P negative eosinophilic foci.

Adenoma, Liver Cell↗

PubMed1998

Slight promotion effects of intermittent administration of testosterone propionate and/or diethylstilbestrol on 3,2'-dimethyl-4-aminobiphenyl-initiated rat prostate carcinogenesis.

In order to determine the effects of intermittent hormonal manipulation on the promotion stage of rat prostate carcinogenesis, testosterone and/or estrogen were administered to F344 rats for 40 weeks after 20-weeks treatment with the prostate carcinogen, 3,2'-dimethyl-4-aminobiphenyl. For this purpose testosterone propionate (TP) and diethylstilbestrol (DES) were introduced into silastic tubes, 2- and 0.5-cm long, respectively, and implanted into the subcutis for seven repeated cycles of 30 days treatment and 10 days withdrawal. Intermittent administration of TP resulted in suppression of ventral prostate adenocarcinoma development and slight but non-significant increases in the incidences of invasive carcinomas of the lateral prostate and seminal vesicles. Intermittent administration of DES completely suppressed tumorigenesis in all sites and the combination of TP and DES generally inhibited prostate tumor development. Thus, under the present experimental conditions, no strong enhancing effects of cyclic hormonal manipulation were observed on rat prostate carcinogenesis. Indeed, the opposite appeared to be the case.

Aminobiphenyl Compounds↗

PubMed1998

Lack of promoting effects of the electromagnetic near-field used for cellular phones (929.2 MHz) on rat liver carcinogenesis in a medium-term liver bioassay.

The possible cancer promotion potential of local exposure to a pulse modulated 929.2 MHz electromagnetic near-field on chemically-initiated rat liver carcinogenesis was investigated employing a medium-term bioassay. A 929.2-MHz electromagnetic near-field of time division multiple access (TDMA) signal for PDC (Personal Digital Cellular, Japanese cellular telephone standard) system was directed to rats through a quarter-wavelength monopole antenna. Maximum local specific absorption rates (SARs) on temporal average were 7.2-6.6 W/kg within the whole body and 2.0-1.7 W/kg within the liver, which was the target organ. The whole-body average SARs on temporal average were 0.80-0.58 W/kg. Temporal peak SARs had three times these values due to the duty ratio of the PDC signal. Exposure was for 90 min a day, 5 days a week, over 6 weeks. The exposure apparatus was specially designed for this experiment, to allow exposure of the lateral mid-section of the rat body to the electromagnetic near-field. Male F344 rats, 6 week-old, were initially (at week 0) given a single dose of diethylnitrosamine (DEN, 200 mg/kg body wt, i.p.). At 2 weeks later, exposure (48 rats) or sham-exposure (48 rats) was started. The exposure of electromagnetic near-fields was performed using the exposure apparatus mentioned above. At week 3, all rats were subjected to a 2/3 partial hepatectomy. At week 8 (i.e. after 6 weeks exposure or sham-exposure), the experiment was terminated and all rats were killed. Carcinogenic potential was scored by comparing the numbers and areas of the induced glutathione S-transferase placental form (GST-P) positive foci in the livers of the exposed and sham-exposed rats. A further group of 24 animals, given only DEN and partial hepatectomy, served as the controls. The numbers (no./cm2) of GST-P positive foci were 4.61 +/- 1.77, 5.21 +/- 1.92 (P < 0.05, versus control) and 4.09 +/- 1.47 and the areas (mm2/cm2) were 0.30 +/- 0.16, 0.36 +/- 0.21 and 0.28 +/- 0.15, for the exposed, sham-exposed and control groups, respectively. There were no significant differences between the exposed and sham-exposed groups. These findings clearly indicated that local body exposure to a 929.2-MHz field, modulated in a PDC waveform, has no significant effect on rat liver carcinogenesis under the experimental conditions employed.

Adrenocorticotropic Hormone↗

PubMed1998

The 1.5 GHz electromagnetic near-field used for cellular phones does not promote rat liver carcinogenesis in a medium-term liver bioassay.

We have recently established that local exposure to a 929.2 MHz electromagnetic near-field, used for cellular phones, does not promote rat liver carcinogenesis in a medium-term bioassay system. In the present study, a 1.439 GHz electromagnetic near-field (EMF), another microwave band employed for cellular phones in Japan, was similarly investigated. Time division multiple access (TDMA) signals for the Personal Digital Cellular (PDC) Japanese cellular telephone standard system were directed to rats through a quarter-wavelength monopole antenna. Numerical dosimetry showed that the peak SARs within the liver were 1.91-0.937 W/kg, while the whole-body average specific absorption rates (SARs) were 0.680-0.453 W/kg, when the time-averaged antenna radiation power was 0.33 W. Exposure was for 90 min a day, 5 days a week, over 6 weeks, to male F344 rats given a single dose of diethylnitrosamine (200 mg/kg, i.p.) 2 weeks previously. At week 3, all rats were subjected to a two-thirds partial hepatectomy. At week 8, the experiment was terminated and the animals were killed. Carcinogenic potential was scored by comparing the numbers and areas of the induced glutathione S-transferase placental form (GST-P)-positive foci in the livers of exposed (48) and sham-exposed rats (48). Despite increased serum levels of corticosterone, adrenocorticotropic hormone (ACTH) and melatonin, the numbers and the areas of GST-P-positive foci were not significantly altered by the exposure. These findings clearly indicated that local body exposure to a 1.439 GHz EMF, as in the case of a 929.2 MHz field, has no promoting effect on rat liver carcinogenesis in the present model.

Adrenocorticotropic Hormone↗

PubMed1998

Medium-term bioassays for carcinogenicity of chemical mixtures.

Carcinogenic effects of chemical mixtures were examined with a medium-term liver bioassay for carcinogens or a multiorgan medium-term bioassay using male F344 rats. In the medium-term liver bioassay, rats were initially treated with diethylnitrosamine (DEN) at 200 mg/kg body weight, i.p.; after 2 weeks they received chemical mixtures such as 10 different heterocyclic amines at one-tenth or one-hundredth the dose levels used in carcinogenicity studies and the mixtures of 20 different pesticides, each at acceptable daily intake (ADI) levels or a mixture of 100 times ADI levels. All animals were subjected to two-thirds partial hepatectomy at week 3 and were sacrificed at week 8. The number and areas of glutathione S-transferase placental form (GST-P) positive foci (preneoplastic lesions in the liver) were compared between respective groups. When 10 heterocyclic amines were mixed in the diet at one-tenth dose level, clear synergism was observed, but no combined effects were evident with the one-hundredth dose levels. In the pesticide experiment, treatment of rats with the 20-pesticide mixture at the ADI dose level did not enhance GST-P-positive foci. In contrast, a mixture of 100 times the ADI significantly increased those values. In a multiorgan bioassay of 28 weeks, mixtures of 40 high-volume compounds and 20 pesticides (suspected carcinogens) added together at their respective ADI levels did not enhance carcinogenesis in any organs initiated by five different carcinogens (DEN, N-methylnitrosourea, dimethylhydrazine, N-butyl-N-(4-hydroxybutyl)nitrosamine, and dihydroxy-di-n-propylnitrosamine) in combination. The combination effect of low dietary levels of five antioxidants, butylated hydroxyanisole, caffeic acid, sesamol, 4-methoxyphenol, and catechol, were also examined using the multiorgan bioassay. The incidence of forestomach papillomas was significantly increased only in the combination group and the results indicate that combination of the five antioxidants can exert additive/synergistic effects on tumorigenesis in the multiorgan bioassay. These results indicate that chemical mixtures at very low doses did not enhance preneoplastic lesions synergistically but the mixtures at certain doses show synergism in the target organ. The medium-term bioassays are particularly useful tools for this purpose.

Animals↗

PubMed1998

Medium-term bioassays as alternative carcinogenicity test.

A medium-term liver bioassay system for rapid detection of carcinogenic agents using male F344 rats has been developed, in order to bridge the gap between long-term carcinogenicity tests and short-term screening assays. The system is fundamentally based on the two-stage hypothesis of carcinogenesis: initiation with diethylnitrosamine (200 mg/kg bw, i.p.) is followed by test chemical administration during the second, in combination with 2/3 partial hepatectomy. It requires only 8 weeks for animal experimental treatment and a further few weeks for quantitative analysis of immunohistochemically-demonstrated glutathione S-transferase placental form positive hepatic foci. A total of 291 chemicals/substances have already been analyzed in this laboratory and the efficacy of the system for hepatocarcinogens has thereby been well established. This bioassay is particularly useful for dose-response and chemical mixture studies, usually requiring large-scale experiments and also for evaluation of chemopreventive agents. Another bioassay, a medium-term multiorgan bioassay system, using 5 different chemical carcinogens, diethylnitrosamine (DEN), N-methylnitrosourea (MNU), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), 1,2-dimethylhydrazine (DMH) and 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN), has also been established for rapid detection of not only hepatocarcinogens, but also other organ-target carcinogens. Rats were initially treated with a single i.p. administration of 100 mg/kg DEN, 4 i.p. administrations of 20 mg/kg MNU, 4 s.c. doses of 40 mg/kg DMH for 2 weeks and then 0.1% DHPN for 2 weeks. Test chemicals are administered after the carcinogens exposure. Animals were sacrificed at the end of week 36, and major organs were examined histologically. Carcinogenic activities of test chemicals were compared between the test chemical treated group and carcinogen exposures group (control group). It is increasingly becoming regarded that these bioassays are useful methods and are appropriate alternative tests systems for carcinogenicity risk assessment. Therefore, 'the International Conference on Harmonization (ICH) of Technical Requirements for the Registration of Pharmaceuticals for Human Use' has proposed that these two bioassays can be used as "additional tests for carcinogenic activity in vivo."

Animals↗

PubMed1997

Carcinogenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the rat.

A total of 10 highly-mutagenic heterocyclic amines have been identified to be carcinogenic in rodents. Among these, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), generally the most abundant with normal cooking procedures, induces mammary and colon carcinomas in rats in a clear dose-dependent manner. In a two-generation exposure (transplacental and trans-breast milk) experiment using Sprague-Dawley rats, an increased risk of mammary adenocarcinoma development was found in the second generation. Excretion of PhIP into the milk and transfer of PhIP to fetuses and neonates with resultant hepatic PhIP-DNA adduct formation were also confirmed. On the other hand, PhIP mammary carcinogenesis was significantly inhibited by coadministration of chlorophyllin or a synthetic antioxidant, 1-O-hexyl-2,3,5-trimethylhydroquinone, in long-term experiments using female F344 rats. The available findings strongly suggest that this food-derived carcinogen might be of importance as an environmental factor in the production of human cancers and that its carcinogenicity could be largely avoided by reducing intake of such compounds or by adoption of appropriate chemopreventive measures.

Adenocarcinoma↗

PubMed1997

The prostate: a target for carcinogenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) derived from cooked foods.

Prostate tissues obtained from rats given a food-derived carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), at a dose of 400 ppm in the diet for 52 weeks were histopathologically evaluated and found to contain prostate carcinomas limited to the ventral lobe in 18 of 27 cases. Atypical hyperplasias were also detected in the ventral and anterior prostate as well as the seminal vesicles. 32P-Postlabeling analysis of DNA demonstrated that PhIP-DNA adducts are produced in all lobes of the prostate of rats receiving PhIP. The findings indicate that PhIP is carcinogenic to rat prostate in addition to the previously demonstrated targeting of the colon and mammary glands, providing evidence of a possible role of PhIP in human prostate carcinogenesis and highlighting the potential importance of PhIP for man.

Animals↗

PubMed1997

Clinicopathological analysis on cancers of autopsy cases in a geriatric hospital.

It is generally accepted that cancers in the elderly are of low grade malignancy. In order to clarify this point, autopsy cases from a medical center for the elderly between 1982 and 1994 were pathologically analyzed. Three hundred and fifty (160 males, 190 females) out of a total of 871 (361 males, 510 females) autopsy cases were examined. The incidence of cancer in various age groups were found to be as follows: < or = 69 years, 24/67 (36%); 70-74 years, 40/102 (39%); 75-79 years, 54/136 (39%); 80-84 years, 79/180 (44%); 85-89 years, 66/172 (38%); 90-94 years, 59/137 (43%); 95-99 years, 17/56 (30%); and > or = 100 years, 12/21 (57%). The incidences did not significantly differ among the groups, that is, there was no age-dependency in the incidence of cancer. Furthermore, the incidences of multiple cancers (two or more different malignancies in one patient) also did not differ. However, deaths due to the cancers showed a tendency to decrease with age. The survival periods of clinical cancer cases without a surgical operation history (time period between the date of diagnosis and death), were age-related for female cases. However, the rate of distant metastasis was not age-related. The incidence of latent cancers in individuals over 85 years of age was 79/174 (45.4%) and significantly higher than the value of 69/234 (29.5%) for those under 85. The number of malignant tumors in various organs for the different age groups was also counted and the total numbers of clinical cancers and latent cancers in each organ were, 50 and 23 in the lung, 46 and 20 in the stomach, 41 and 31 in the colon, 0 and 39 in the prostate, and 14 and 0 in the mammary glands, respectively. All prostate cancers were latent cancers, and all mammary cancers were clinical cancers. These findings provide strong evidence that cancers in individuals of advanced age have less malignancy potential.

Age Distribution↗

PubMed1996

Medium-term liver and multi-organ carcinogenesis bioassays for carcinogens and chemopreventive agents.

To bridge the gap between long-term carcinogenicity tests and short-term screening assays such as the Ames test, several types of medium-term bioassay for rapid detection of carcinogenic agents have been developed using male F344 rats. The liver model, in which diethylnitrosamine initiation and acceleration of carcinogenesis by partial hepatectomy are essential components, requires only 8 weeks of animal experimentation and a few weeks for quantitative analysis of hepatic preneoplastic lesions. Using the model, a total of 250 chemicals have been analyzed and the efficacy of the system for hapatocarcinogens has thereby been well established. Other models are so-called multi-organ bioassays for detection of carcinogenic agents in multiple organs within relatively short periods. Among these, the DMBDD bioassay with 5 known carcinogens as initiators has been found to be most applicable and has now been introduced for practical use. Data from these bioassays and several single organ carcinogenesis systems have demonstrated that carcinogenic and modifying effects of individual exogenous agents may markedly differ from organ to organ. Therefore, research into chemoprevention should be based on a whole body level analysis. The present medium-term systems are very useful for this purpose.

Animals↗

PubMed1996

Chemically induced lung and forestomach neoplasias in transgenic mice carry mutant forms of the human c-Ha-ras transgene.

Susceptibility to lung carcinogens and genetic changes in neoplastic lesions were investigated in transgenic mice carrying a human hybrid c-Ha-ras gene, encoding a prototype p21 gene product. Nine-week-old male and female transgenic mice and non-transgenic littermates were injected i.p. with 6-nitrochrysene (6NC) three times biweekly or administered urethane in their drinking water for 3 weeks. Control mice were given dimethylsulfoxide (DMSO), the solvent for 6NC, alone. The incidences of lung adenocarcinomas were four out of seven female (57%) transgenic mice treated with 6NC and three out of three males (100%) and three out of three females (100%) receiving urethane. No adenocarcinomas were observed in control animals or non-transgenic mice. Adenomas developed in all treated groups, but the incidence and multiplicity were higher in transgenic animals than in their non-transgenic counterparts. In the 6NC-treated group, forestomach papillomas and squamous cell carcinomas were also observed in both male (25 and 50%) and female (56 and 33%) transgenic mice. PCR-SSCP and DNA sequence analysis of these induced lesions revealed point mutations at codon 61 of transgenic human c-Has-ras, from CAG (Gln) to CTG (Leu) or CAG (Gln) to AAG (Lyn) in lung hyperplasias (two out of three), an adenoma (one out of two), adenocarcinomas (five out of seven) and forestomach squamous cell carcinomas (four out of five). Mutations were not observed in forestomach papillomas. No changes in mouse Ha-ras or Ki-ras were found in any lesions. Furthermore, p21 overexpression was not evident in lung or forestomach tumors on immunohistochemical analysis. These findings indicate a high sensitivity to lung carcinogens in transgenic mice carrying the human c-Ha-ras gene and that this might be effected by mutational activation.

Animals↗

PubMed1996

Direct effects of testosterone, dihydrotestosterone and estrogen on 3,2'-dimethyl-4-aminobiphenyl-induced prostate carcinogenesis in castrated F344 rats.

The present experiment was carried out to explore the effect of endogenous androgen on rat prostate carcinogenesis induced by 3,2'-dimethyl-4-aminobiphenyl (DMAB) and testosterone propionate (TP) or 5alpha-dihydrotestosterone (DHT) with or without ethinyl estradiol (EE). In order to eliminate the influence of endogenous androgen, F344 rats were orchiectomized just after initiation with the prostate carcinogen, DMAB, and then given TP, DHT, TP plus EE or DHT plus EE for 40 weeks. The results demonstrated that while administration of TP following DMAB treatment causes invasive carcinomas in the lateral and anterior prostate and seminal vesicles, DHT does not exhibit equivalent effects. Synergistic enhancement was also evident with TP plus EE, but not with DHT plus EE. The incidences of prostatic and seminal vesicle lesions in all groups of the present experiment, except for the group given castration without hormonal supplement, were equivalent to those previously found in non-castrated animals. Therefore, the present findings indicate that endogenous testosterone may not be required for promotion by TP/EE of DMAB-initiated prostate carcinogenesis and that it may not contribute to the actions of DHT.

Aminobiphenyl Compounds↗

PubMed1996

Dose-dependent induction of mammary carcinomas in female Sprague-Dawley rats with 2-amino-1-methyl-6-phenylimidazol[4,5-b]pyridine.

The dose-dependence of 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induction of mammary carcinomas was investigated in female Sprague-Dawley (SD) rats given PhIP in the diet for 48 weeks at concentrations of 0, 25, 100 and 200 ppm in experiment 1, and 0, 12.5, 50 in experiment 2. Yields of ductular lesions, including intraductal papillomas and carcinomas, as well as papillo-tubular and solid-tubular carcinomas, showed dependence on the dose, with the respective total incidences being 0, 4.8, 25, 72.2 and 0, 10 and 35%. There was thus no apparent carcinogen exposure threshold. The present results confirmed the carcinogenicity demonstrated in a previous study using F344 rats and revealed the SD rat strain to be more susceptible.

Adenocarcinoma↗