Short interpregnancy interval after B-Lynch uterine compression suture: a case report.

PURPOSE: The influence of the B-Lynch suture technique on subsequent fertility and pregnancy outcomes is not clear. In the present report, the authors describe the case of a very short interpregnancy interval following the successful placement of a B-lynch suture and discuss the associated problems. MATERIALS AND METHODS: A 33-year-old-woman underwent cesarean section after undergoing artificial induction of labor and subsequent atonic postpartum hemorrhage. Placement of a B-Lynch brace suture successfully stopped the bleeding and preserved the uterus. The patient became unexpectedly pregnant only four months later, making the present case the shortest reported interpregnancy interval after a surgery involving the B-Lynch suture. CONCLUSION: In the present case, fertility was not affected, and obstetric complications (abortion, fetal growth restriction, preterm delivery, and placenta previa) were not observed. Adhesions between the abdominal wall and the surface of the uterus along the previous B-Lynch suture line were observed and irregular, large blood vessels were observed on the surface of the uterus. Further reports are expected to determine the influence of the B-Lynch brace suture technique on the subsequent pregnancy.

Retrospective analysis of the survival benefit of chemotherapy for recurrent or advanced epithelial ovarian carcinoma in patients previously treated with paclitaxel plus platinum-based chemotherapy.

AIM: The outcomes of treatment for women with recurrent or advanced epithelial ovarian carcinoma previously treated with pacli- taxel plus platinum-based chemotherapy were analyzed. MATERIALS AND METHODS: Retrospective analysis was performed in a total of 65 series of treatments provided for 35 patients with a history of paclitaxel plus platinum-based chemotherapy. The chemotherapy regimens used were classified into the following four types for analysis: conventional paclitaxel plus carboplatin therapy (TC arm), pegylated liposomal doxorubicin-containing regimens (PLD arm), CPT-11-containing regimens (CPT-11 arm), and others. Disease-control rates (DCRs) were compared and subjected to univariate analysis. Progression-free survival (PFS) was determined from the date of the first cycle of each chemotherapy with the Kaplan-Meier method, and comparisons were performed using the log-rank test. RESULTS: DCR was 80%, 71%, and 26% for the TC, PLD, and CPT-l arms, respectively. The median PFS was 286, 372, and 76 days for the TC, PLD, and CPT-11 arms, respectively. There was no discernible difference in PFS between the TC and the PLD arm. In contrast, PFS of the CPT- 11 arm was significantly shorter than that of the TC and PLD arms. In addition, three of seven (42.9%) treatments in the PLD arm maintained a progression-free period for longer than one year, while only one of 25 (4%) treatments in the TC arm maintained a progression-free period for more than one year. CONCLUSIONS: The PFS of PLD is similar to that of TC. PLD-containing regimens might have a potential benefit with a higher PFS over one year than the TC regimen.

The effects of long-term exposure to ozokerite mainly consisting of an aliphatic series of hydrocarbons using F344 rats.

Combined chronic toxicity and carcinogenicity studies of ozokerite (OZK), a natural wax substance used as a food additive for a gum base, were performed in male and female F344 rats. Dietary concentrations of 0%, 0.05%, 0.1% and 0.2% OZK were applied in a 52-week chronic toxicity study and 0%, 0.1% and 0.2% in a 104-week carcinogenicity study. In the chronic toxicity study, treatment with OZK caused a xenobiotic reaction against absorbed OZK, including formation of histiocytosis and granulomas with crystalline material in many organs in all of the treated males and females. Particularly in the liver, granulomatous inflammation was accompanied by hepatocellular vacuolation and changes in the serum biochemical parameters indicative of hepatic disorder. The number and area of glutathione S-transferase placental form (GST-P) positive foci were increased in all of the treated groups of both sexes, suggesting the proliferative effect of OZK. In the carcinogenicity study, the incidence of hepatocellular adenoma and the total tumor incidence in the liver of all of the treated males were significantly increased compared with the controls. In conclusion, long-term exposure to OZK caused systemic chronic inflammation due to a foreign body response. OZK was weakly carcinogenic in the liver of male F344 rats.

Comprehensive toxicity study of safrole using a medium-term animal model with gpt delta rats.

In order to investigate a medium-term animal model using reporter gene transgenic rodents in which general toxicity, genotoxicity and carcinogenicity are evaluated, F344 gpt delta rats were given a diet containing 0.1% and 0.5% (a carcinogenic dose) safrole for 13 weeks. Serum biochemistry and histopathological examinations revealed overt hepatotoxicity of safrole, in line with previous reports. In the current study, safrole treatment possibly resulted in renal toxicity in male rats. In the in vivo mutation assays, an increase or a tendency to increase of the gpt mutant frequencies (MFs) was observed in both sexes at the carcinogenic dose. The number and area of foci of glutathione S-transferase placental form (GST-P) positive hepatocytes, ratio of proliferating cell nuclear antigen (PCNA)-positive hepatocytes and 8-hydroxydeoxyguanosine (8-OHdG) levels in liver DNA were significantly increased in both sexes of the 0.5% group. The overall data suggested that the present model might be a promising candidate for investigating comprehensive toxicities of the agents. In addition, data demonstrating the base modification and cell proliferation due to exposure to safrole could contribute to understanding safrole-induced hepatocarcinogenesis, which imply expanding in application of this model.

Investigation of carcinogenicity for levamisole administered in the diet to F344 rats.

A two year carcinogenicity study of anthelmintic drug levamisole (LV) was performed using 50 male and 50 female F344 rats at dietary drug concentrations of 0, 60, or 300 ppm. The daily intakes of LV were calculated to be 2.6, 12.9 mg/kg b.w./day for males and 2.9, 14.1mg/kg b.w./day for females, respectively. No significant differences in general condition and survival rate (82%, 74%, 80% in males and 84%, 84%, 84% in females, respectively) were observed. In the 300 ppm group, suppression of body weight gain was observed from the onset of treatment and reduction in final body weights was 6% in males and 11% in females. Significant increases in the absolute and/or relative weights of the lungs, heart, spleen, liver, kidneys, and adrenals were observed in males and/or females treated with 300 ppm. Some of high incidences neoplasms were observed, and there were also tendencies to increase for mammary gland fibroma and thoracic/abdominal cavity mesothelioma in males. However, there were no significant inter-group differences in incidences, histopathological types or differences compared with historical control data. Thus, it was concluded that LV was not carcinogenic to male and female F344 rats under the experimental conditions.

Safety assessment of dietary administered paprika color in combined chronic toxicity and carcinogenicity studies using F344 rats.

Combined chronic toxicity and carcinogenicity studies of paprika color, used as a food additive in various countries, were performed in male and female F344 rats. Dietary concentrations of 0%, 0.62%, 1.25%, 2.5% and 5% were applied in a 52-week toxicity study and 0%, 2.5% and 5% in a 104-week carcinogenicity study. Treatment with paprika color caused a significant increase in incidence of hepatocellular vacuolation in 5% males, but no toxicological effects were found with reference to survival rates, body weights, hematological or serum biochemical parameters and organ weights at any dose level in either sex in the chronic toxicity study. Also, paprika color did not induce specific tumors nor did it exert significant influence on the development of spontaneous tumors in any of the organs examined in the carcinogenicity study. In conclusion, based on slight histopathological changes observed in 5% male livers, the no-observed-effect level (NOEL) was estimated to be 2.5% in the diet (1,253 mg/kg bw/day) and the no-observed-adverse-effect level (NOAEL) was determined to be 5% in the diet (2,388 mg/kg bw/day) for male rats, and for females, the NOEL was concluded to be 5% in the diet (2,826 mg/kg bw/day). Additionally, paprika color was not carcinogenic to male and female F344 rats under the present experimental conditions.

Lack of chemopreventive effects of alpha-eleostearic acid on 7,12-dimethylbenz[a]anthracene (DMBA) and 1,2-dimethylhydrazine (DMH)-induced mammary and colon carcinogenesis in female Sprague-Dawley rats.

alpha-Eleostearic acid is one of the conjugated linolenic acids from tung oil, which is obtained from the seeds of Aleurites fordii. The effects of dietary alpha-eleostearic acid (18:3, n-5) on the post-initiation period of 7,12-dimethylbenz[a]anthracene (DMBA) and 1,2-dimethylhydrazine (DMH)-induced mammary and colon carcinogenesis were examined using female Sprague-Dawley (SD) rats. For initiation, rats were given subcutaneous injections of 40mg/kg body weight (5 times) and 20mg/kg body weight (3 times) of DMH during the age of 6-8 weeks and a single intragastric administration of 50mg/kg body weight of DMBA at 9 weeks. Then, the animals were treated with 0%, 0.01%, 0.1% or 1.0% alpha-eleostearic acid for 34 weeks. Control rats received the basal diet alone or 1.0% alpha-eleostearic acid without prior initiation treatment. All surviving animals were killed at week 37 of the experiment. There were no statistically significant alterations in any of the parameters for either mammary or colon tumors. These results thus indicate that alpha-eleostearic acid does not exert clear modification effects on DMBA and DMH-induced mammary and colon carcinogenesis, at least under the present experimental conditions.

Detection of API2-MALT1 fusion transcripts in cytologic specimens of patients with pulmonary mucosa-associated lymphoid tissue lymphoma.

Mucosa-associated lymphoid tissue (MALT) lymphoma constitutes up to 90% of primary pulmonary lymphomas, but its diagnosis is often difficult. API2-MALT1 fusion is specific to MALT lymphoma and is detected in nearly half of the pulmonary cases. Cytologic examinations have played a pivotal role in the diagnosis of pulmonary tumors; however, cytologic specimens have only infrequently been used for molecular studies. In this study, we performed a multiplex reverse transcription-polymerase chain reaction (RT-PCR) assay to detect the API2-MALT1 fusion transcript in archival cytologic specimens used as RNA sources. We studied 3 pulmonary MALT lymphoma cases that were positive for the fusion gene as detected with RNA extracted from diagnostic histologic specimens. In 1 case, a conventional PCR clonality assay for the immunoglobulin heavy chain gene rearrangement failed to detect the monoclonality. In all 3 cases, the fusion transcript was successfully detected in the cytologic specimens of sputum, bronchoalveolar lavage fluid, bone marrow smears, and pleural effusions. This finding suggests that such specimens can be used as RNA sources in multiplex RT-PCR assays for the API2-MALT1 fusion transcript. The detection of API2-MALT1 fusion as carried out with these specimens would be useful as an ancillary assay for the diagnosis, staging, and follow-up of pulmonary MALT lymphoma.

Lack of carcinogenicity of D-xylose given in the diet to F344 rats for two years.

The two year carcinogenicity of D-xylose was examined in groups of 50 male and 50 female F344 rats at dietary doses of 0% (control), 2.5% and 5%. The doses were selected on the basis of results from a 13-week subchronic toxicity study. Growth suppression and soft feces were observed in male and female rats of the 5% group. However, no significant differences from the controls were noted with regard to clinical signs, mortality and hematological findings. Decrease in absolute weight and increase in relative weight of the brain in males, and decrease of absolute kidney weight in females were observed in the 5% group, but there were no remarkable histopathological changes. A variety of tumors developed in all groups, including the controls, but all were histologically similar to those known to occur spontaneously in F344 rats, and no statistically significant increase in the incidence of any type of neoplastic lesion was found for either sex in the treated groups. Thus, it was concluded that, under the present experimental conditions, D-xylose is not carcinogenic to F344 rats.

Lipoteichoic acid from Staphylococcus aureus enhances allergen-specific immunoglobulin E production in mice.

BACKGROUND: Our previous study demonstrated that lipoteichoic acid (LTA) from Staphylococcus aureus induced T helper type 2 (Th2)-prone dermatitis resembling that seen in atopic dermatitis (AD) patients in mice sensitized percutaneously with an allergen. However, the effects of LTA on allergen-specific IgE production in such sensitized mice have not been elucidated. OBJECTIVE: The purpose of this study was to determine the effects of LTA from S. aureus on allergen-specific IgE production in mice sensitized percutaneously with a house dust mite antigen (MA). METHODS: Mice were sensitized with a single topical application of MA and/or LTA to barrier-disrupted abdominal skin. One to 5 weeks later, MA-specific IgE antibodies in sera from sensitized mice were detected by an enzyme-linked immunosorbent assay (ELISA). Expression of B7.1 (CD80), B7.2 (CD86) and CD40L molecules by CD40-positive (CD40+) and CD4-positive (CD4+) cells in the lymph nodes of sensitized mice were analysed by flow-cytometry (FACS). RESULTS: Simultaneous sensitization with MA and LTA increased IgE production 3 weeks later, significantly more than sensitization with MA alone. FACS analysis of CD40+ cells in the lymph nodes from sensitized mice showed that simultaneous sensitization with MA and LTA did not enhance CD80- or CD86-expression by antigen-presenting cells such as B lymphocytes and dendritic cells more than sensitization with MA alone. However, analysis of CD4+ cells in the lymph nodes showed that simultaneous sensitization with MA and LTA increased the number of CD40L-expressing Th cells more than sensitization with MA alone. CONCLUSION: These results suggest that LTA enhances allergen-specific IgE production by a mechanism associated with up-regulation of CD40L-expressing Th cells and this might explain the role of skin colonization with S. aureus in AD patients.

Spontaneous development of aberrant crypt foci in F344 rats.

Aberrant crypt foci (ACF) have been proposed as intermediate biomarkers for colon carcinogenesis on the basis of many rodent studies. Although molecular analyses have indicated that these lesions in experimental animals are related to early events in colon carcinogenesis, their preneoplastic nature has yet to be fully elucidated. In the present study, one hundred and thirty 19-week-old male Fischer 344 rats were examined. The biological characteristics of spontaneous ACF were analyzed histopathologically, immunohistochemically and with molecular biological techniques, and compared with colon tumors found in control groups used for carcinogenicity tests. The incidences of spontaneous ACF consisting of 1, 2, 3 and 4 or more crypts were respectively 27.7%, 32.5%, 16.8% and 22.8%. Most ACF were distributed in the lower middle and upper distal colon, and proximal colon ACF was rare. Likewise, ACF frequently (42.5%) developed in untreated animals, whereas the incidence of spontaneous colorectal tumors was extremely low (0.68%) in control male rats. In addition, spontaneous ACF did not show apparent proliferative activity or c-K-ras point mutations. Our results thus suggest that spontaneous ACF rarely progress to colon tumors although long-term sequential observation might be necessary to conclude the significance of ACF.

Cyclic changes in expression of mRNA of vascular endothelial growth factor, its receptors Flt-1 and KDR/Flk-1, and Ets-1 in human corpora lutea.

OBJECTIVE: To evaluate the expression of mRNA of vascular endothelial growth factor (VEGF), its receptors Flt-1 and KDR/Flk-1, and Ets-1 in human corpora lutea. DESIGN: Prospective laboratory study. SETTING: University hospital in Japan. PATIENT(S): Women with regular menstrual cycles who underwent hysterectomy. INTERVENTION(S): Fifteen corpora lutea were obtained during hysterectomy (5 in the early luteal phase, 5 in the mid-luteal phase, and 5 in the late luteal phase). MAIN OUTCOME MEASURE(S): Expression of VEGF, Flt-1, KDR/Flk-1, and Ets-1 in human corpora lutea on northern blot analysis or immunohistochemistry. RESULT(S): Human corpora lutea in early luteal phase and mid-luteal phase had high VEGF mRNA expression. Expression of VEGF mRNA was significantly reduced in the late luteal phase. Immunohistochemistry showed that VEGF protein was expressed mainly in granulosa lutein cells and faintly in thecal lutein cells. Staining of VEGF protein was decreased in human corpora lutea in the late luteal phase. Expression of Flt-1 and KDR/Flk-1 mRNA was increased in the early luteal phase and mid-luteal phase and decreased in the late luteal phase. Immunohistochemistry showed that Flt-1 and KDR/Flk-1 proteins were expressed mainly in granulosa lutein cells and faintly in thecal lutein cells and endothelial cells in the early luteal phase and mid-luteal phase; their protein staining was reduced in the late luteal phase. Expression of Ets-1 mRNA changed similarly to VEGF and its receptor mRNA in human corpora lutea during the luteal phase. CONCLUSION(S): Levels of mRNA of VEGF and its receptors Flt-1 and KDR/Flk-1 in human luteal cells may be related to luteal function.

Essential similarities between spontaneous and MeIQx-promoted aberrant crypt foci in the F344 rat colon.

Aberrant crypt foci (ACFs) in the Fischer 344 (F344) rat colon, of control or 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)-treated groups, were compared morphologically, immunohistochemically, and at the molecular biological level in order to elucidate their biological characteristics. Male 3-week-old rats were fed a diet supplemented with or without MeIQx at doses of 100 ppm or less for 16 weeks. The incidence of ACFs was the highest (90%) in animals given 100 ppm MeIQx but that in untreated rats was also surprisingly high (57%). Nine ACFs from nine MeIQx-treated rats and ten ACFs from ten untreated control rats were selected for detailed examination for their large size. There were no morphological differences in macroscopic and microscopic features between MeIQx-promoted and spontaneous ACFs. There were also no differences in immunohistochemical labeling for proliferating cell nuclear antigen (PCNA) and p53 protein between these ACFs although in both cases labeling was higher than in normal crypts. Dot blot hybridization revealed no c-K-ras mutations in codon 12 except in one ACF (11.1%) developing in a rat treated with 100 ppm MeIQx, in which a GGT-->GAT single base substitution was detected. Our results thus suggest that in terms of morphology, cell proliferation, P53 expression and c-K-ras mutation, most ACFs found in rats given 100 ppm MeIQx are essentially identical to their spontaneous counterparts.

Evaluation of central nervous system involvement in nasal lymphomas.

OBJECTIVES: To clarify the usefulness of evaluating central nervous system (CNS) involvement in patients with nasal lymphomas at the initial staging procedure, and of CNS prophylaxis for patients with clinical stage I/II. PATIENTS AND METHODS: We retrospectively reviewed 43 patients with nasal lymphomas who had been treated from 1973 through 1999. The staging procedure included mainly computed tomography (CT), ultrasonography, gallium scintigraphy, upper gastrointestinal study, magnetic resonance (MR) imaging, and bone marrow biopsy. Forty-two patients received radiotherapy, and 25 patients received chemotherapy. All 38 patients with stage I/II were not subjected to CNS prophylaxis. RESULTS: Four patients demonstrated CNS involvement at the staging procedure. MR imaging demonstrated the tumor had directly infiltrated the skull base in 3 patients, but CT demonstrated CNS infiltration in only one patient. In another patient, cerebrospinal fluid (CSF) cytologic analyses demonstrated CNS involvement, but MR imaging and CT did not. These 4 patients complained of frontonasal pain and/or cerebral nerve dysfunction. No patient with stage I/II developed CNS relapse. CONCLUSIONS: MR imaging and CSF cytologic analyses should be performed at the initial staging of nasal lymphomas, especially in patients with frontonasal pain and/or cerebral nerve dysfunction. Patients with stage I/II might not need CNS prophylaxis.

Induction of pancreatic islet cell tumors in rats by repeated intravenous administration of 4-hydroxyaminoquinoline 1-oxide.

The inducibility of pancreatic islet cell tumors by administration of 4-hydroxyaminoquinoline 1-oxide (4HAQO) was investigated in male 6-week-old Sprague-Dawley rats. Rats were given 4HAQO intravenously at a weekly dose of 5 mg/kg 4 times (group 1) or a single dose of 10 mg/kg (group 2). Control rats received the vehicle alone (group 3). Fifty-six weeks after the first 4HAQO administration, all surviving animals were killed and the pancreas was examined histopathologically, immunohistochemically and ultrastructurally. The incidences and multiplicities of islet cell tumors in groups 1, 2, and 3 were 52.3% (p < 0.05 vs group 2, p < 0.01 vs group 3), 19.2% and 0%, and 0.70/animal (p < 0.05 vs group 2, p < 0.01 vs group 3), 0.23 and 0, respectively. Islet cell carcinomas were induced only in group 1, accounting for 6/44 (26%) tumors. Islet cell hyperplasias were found in 61.4% (p < 0.05 vs group 3), 42.3% and 10.0% of groups 1, 2, and 3, with multiplicities of 0.95 (p < 0.05 vs groups 2 and 3), 0.54 and 0.20, respectively. As compared with normal islets from control subjects, islet cell tumors showed an increase in the number of insulin positive cells associated with cytological features indicative of enhanced insulin synthesis and secretion, and a decrease in the number of glucagon positive cells without ultrastructural signs of modified secretory activity. Thus our results indicate that repeated intravenous administration of 4HAQO to rats is useful for the induction of islet cell tumors at high incidence.

Promotion of chemically induced rat esophageal tumorigenesis with post-initiation ethanol modification.

Post-initiation ethanol modification on N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal carcinogenesis model was investigated in male, 6-week-old, F344 rats that received s.c. injections, 3 times per week, of 0.5 mg/kg NMBA for the first 5 weeks and then were treated with 0% (Group 1), 3.3% (Group 2), and 10% (Group 3) ethanol in the drinking water for up to 20 weeks. Group 4 received 10% ethanol without NMBA administration and Group 5 was maintained without any chemical treatment. There were no statistical differences in the incidence and multiplicity of esophageal tumors among Groups 1 to 3. However, the multiplicity of hyperplasias was statistically greater in Group 3 than in Groups 1 or 2. Esophageal epithelia of all rats in Groups 4 and 5 demonstrated a normal histology. BrdU labelling indices of tumors and hyperplasias in NMBA-treated groups were essentially similar, although cycline D1 was overexpressed to a greater extent in tumors and also hyperplasias of Group 3 than in Groups 1 or 2. The results indicated ethanol to exert weak promotion effects through cycline D1 overexpression on rat esophageal tumorigenesis initiated with NMBA.

Synergistic effects of high-dose soybean intake with iodine deficiency, but not sulfadimethoxine or phenobarbital, on rat thyroid proliferation.

The specificity and dose dependence of the synergistic effects of soybean intake with iodine deficiency on the induction of thyroid proliferation were investigated in female F344 rats. In the first experiment, rats were divided into 6 groups, each consisting of 5 animals, and fed a basal diet containing 20% gluten, an iodine-deficient basal diet alone or an iodine-deficient diet containing 0.2%, 1.0%, 5.0% or 25% defatted soybean for 5 weeks. Soybean feeding synergistically induced thyroid hyperplasias with iodine deficiency only at the 25% dose. In the second experiment, rats were also divided into 6 groups, each consisting of 5 animals, and fed a basal diet, a diet containing 20% defatted soybean, 0.025% sulfadimethoxine (SDM), 20% defatted soybean + 0.025% SDM, 0.05% phenobarbital (PB) or 20% defatted soybean + 0.05% PB for 5 weeks. The SDM treatments significantly (P < 0.05 - 0.01) increased the thyroid weights, but this increase rate was less prominent in the SDM + soybean group than in the SDM alone group. The PB treatment was also associated with a tendency for increase in thyroid weight, but again this was smaller in the PB + soybean group than in the PB alone group. Although the SDM or PB treatments reduced the serum triiodothyronine and thyroxine levels and consequently increased the serum thyroid-stimulating hormone (TSH) levels, the soybean feeding did not affect or rather attenuated these changes. Our results clearly indicate that soybean feeding does not synergistically enhance the effects of SDM or PB on the rat thyroid. Thus it can be concluded that soybean intake specifically interacts with iodine deficiency in induction of thyroid proliferative lesions in rats, only at high doses.

Reporter gene transgenic mice as a tool for analyzing the molecular mechanisms underlying experimental carcinogenesis.

Carcinogenic compounds are classified into 2 categories, genotoxic and non-genotoxic, which are basically judged from in vitro genotoxicity data. However, it is well documented that genotoxicants do not necessarily exert in vivo carcinogenicity in rodents, partly because of a discrepancy between in vitro and in vivo mutagenicities. Recently, transgenic animal models with reporter genes such as lacI, lacZ and gpt have been developed as a tool for assessing in vivo mutagenicity as well as carcinogenicity. In this article, data using lacI transgenic mice and gpt delta mice are presented and their application is discussed. In lacI transgenic mice, dimethylnitrosamine (DMN) treatment significantly increased lacI mutant frequency (MF) in the liver, kidenys and lungs, but not in other non-target organs. Repeated dose ip administration of DMN was more effective than single dose treatment in the induction of lacI MF. The spectrum of mutant plaques induced by DMN was characterized by deletions as well as GC to AT base transitions. The remaining mice receiving DMN proved to have liver adenomas at a high frequency after 78 weeks. Meanwhile, dietary 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) significantly increased lacI and gpt MFs in the liver and colon. The characteristic spectrum of mutant plaques induced by MeIQx was a GC to TA base transversion in both the lacI and gpt mutations. Our results thus strongly suggest that these reporter gene transgenic animal models could offer a useful tool for analyzing molecular mechanisms underlying experimental carcinogenesis and for assessing the carcinogenic risk of environmental chemicals.