Biomedical subjects

J M Ward

Publications and source records attributed to J M Ward.

At least 271 records · Page 15Linked to original sources

PubMed1986

The chronic hepatotoxic, tumor-promoting, and carcinogenic effects of acetaminophen in male B6C3F1 mice.

Acetaminophen (ACT), the most commonly used analgesic and antipyretic in the United States, was previously demonstrated to be a hepatocarcinogen in one mouse study but not in rats. In order to help elucidate the potential mechanisms of carcinogenesis by this nongenotoxic chemical and its relationship to hepatotoxicity, ACT was fed to groups of 60-120 male B6C3F1 mice at dietary concentrations of 5000 or 10,000 ppm from 6 weeks of age for periods of up to 70 weeks to study the hepatotoxic effects of ACT. To test for potential liver tumor-promoting effects of ACT, N-nitrosodiethylamine (DEN) was injected intraperitoneally at 40 mg/kg into additional groups of 30-60 male B6C3F1 mice at 4 weeks of age. Two weeks later some mice received ACT at dietary concentrations of 5000 or 10,000 ppm. Mice were sacrificed either at 24 weeks after DEN injection or after 22 or 70 weeks of ACT exposure. The livers were weighed and prepared for qualitative and quantitative histological evaluation of focal hepatocellular proliferative lesions (FHPL) including microscopic hyperplastic foci and neoplasms by automated image analysis. At 24 weeks the incidence and number of FHPL per square centimeter were significantly increased only in DEN-treated mice receiving 10,000 ppm ACT. Chronic hepatotoxicity was mild at this time. At 72 weeks ACT alone had no effect on the incidence or number of naturally occurring liver tumors despite severe chronic hepatotoxicity and suppression of body weight gain in mice receiving 10,000 ppm and only mild toxicity at 5000 ppm. There were histological findings suggesting that the chronic hepatotoxicity had, in part, a vascular pathogenesis. This study provided evidence against the hypothesis that chronic hepatotoxicity, in and of itself, results in an increased incidence of naturally occurring liver tumors in mice.

Acetaminophen↗

PubMed1986

Association between carcinogenic potency and tumor pathology in rodent carcinogenesis bioassays.

Carcinogenic potency (TD50) estimated from the results of 88 NCI/NTP carcinogenesis bioassays was examined by common target sites in rats and mice. Other indicators of a chemical's hazard were investigated, including whether tumors were induced at more than one site in a single sex-species group of test animals, whether tumors may have caused the death of the animal or were found at sacrifice, and whether metastases of induced tumors occurred. These hazard indicators are sometimes interrelated; however, the potency (TD50) values of chemicals which are hazardous by each of these measures spanned a wide range. Carcinogens which caused some type of fatal tumor were more likely than other carcinogens to cause tumors in multiple organ sites and multiple sex-species groups. Since these other hazard indicators were not related to carcinogenic potency, they should be included along with potency estimates such as the TD50 in summarizing the potential dangers of human exposures to a carcinogen and in comparisons of hazard among carcinogens.

Animals↗

PubMed1986

Interstrain differences in susceptibility to liver carcinogenesis initiated by N-nitrosodiethylamine and its promotion by phenobarbital in C57BL/6NCr, C3H/HeNCrMTV- and DBA/2NCr mice.

Selected inbred strains of mice were compared with respect to their susceptibility to two-stage liver carcinogenesis. Five-week-old male mice of strains C57BL/6NCr (C57), C3H/HeNCrMTV- (C3H) and DBA/2NCr (DBA) were given a single i.p. injection of N-nitrosodiethylamine (DEN, 90 mg/kg body weight) or the solvent tricaprylin (10 ml/kg). Beginning 2 weeks later, half of the DEN-treated and half of the control mice were given drinking water containing 0.05% phenobarbital (PB). Ten mice from each treatment group were killed at 12, 24, 36 and 52 weeks of age (5, 17, 29 and 45 weeks exposure to PB). PB significantly increased both the number of hepatocellular foci/cm2 and the incidence of hepatocellular tumors after 17 weeks of treatment in 24-week-old DEN-initiated mice of strains C3H (0.11 +/- 0.07 versus 2.9 +/- 0.3 foci/cm2 and 20 versus 70% incidence of hepatocellular tumors) and DBA (0.09 +/- 0.09 versus 3.72 +/- 0.6 foci/cm2 and 0 versus 90% incidence of hepatocellular tumors) but was ineffective in C57 mice (0.04 +/- 0.04 versus 0.07 +/- 0.07 foci/cm2). At 36 weeks of age the incidence of liver cell tumors in mice given DEN but not PB was 10 (DBA), 10 (C57) and 50% (C3H); the incidence was increased by PB to 90% in DBA and 100% in C3H mice, but there was no increase in C57 mice. Even at 52 weeks, the low incidence of hepatocellular tumors in C57 mice given DEN only (20%) was not significantly increased by subsequent exposure to PB. Serum PB levels observed at 12, 24 and 36 weeks of age were significantly higher in DBA mice than in C57 or C3H mice. Similar results were observed in a separate study in which PB was administered in drinking water to 7-week-old male mice of these three strains for 20 days, during which period serum PB levels were measured at shorter intervals. DBA mice thus appear to be unable to metabolize PB, which itself rather than its metabolites is probably responsible for tumor-promoting effects. DBA mice were especially sensitive, while C57 mice were refractory to promotion of hepatocarcinogenesis by PB. These two strains, which differ with respect to other significant parameters for chemical carcinogenesis including inducibility for aryl hydrocarbon hydroxylase and susceptibility to promotion of hydrocarbon-initiated skin tumors by 12-O-tetradecanoylphorbol-13-acetate, thus also provide a means for analysis of the pharmacogenetics of susceptibility to hepatocellular tumor promotion.

Animals↗

PubMed1986

Immunocytochemical localization of RasHa p21 in normal and neoplastic cells in fixed tissue sections from Harvey sarcoma virus-infected mice.

An affinity purified sheep IgG antibody to a 20 amino acid peptide from the carboxyterminal end of RasHa p21 was used to localize RasHa p21 on fixed tissue sections of Harvey sarcoma (HaSV) virus-infected mice by the avidin-biotin-peroxidase immunocytochemical technique. Control sera included immune sheep sera absorbed with the peptide, preimmune sheep sera and a goat polyclonal antibody to Rauscher leukemia virus p30. Neonatal BALB/c mice were injected with HaSV/Moloney leukemia virus (MoLV), MoLV alone or buffer. Short-term fixation in Bouin's fixative was found to be the most effective method for demonstrating p21 in fixed tissue sections. RasHa p21 was found in 5-80% of the induced sarcoma cells, depending on the tissue fixative and antibody dilution. The antigen was localized to the cell membrane and in the cytoplasm. Tumors induced by NIH 3T3 cells transformed with cellular Ha-ras oncogenes had less than 1% immunoreactive tumor cells. Splenic erythroblasts in HaSV-induced erythroblastosis contained membrane antigen as did some reticular cells in lymph nodes draining the sarcomas. Normal tissues of virus-inoculated mice, uninoculated controls or fetuses and selected naturally occurring or induced liver tumors of mice, chemically induced skin tumors of mice, N-nitrosomethylurea-induced mammary tumors of rats, and naturally occurring tumors of F344/NCr rats did not contain immunoreactive p21. Thus, with the use of affinity purified IgG sheep polyclonal antibody to a peptide in RasHa p21, we were able to demonstrate RasHa p21 in tumors and other cells. The degree of immunoreactivity was related to the expected level of p21 expression.

Animals↗

PubMed1986

Tumor-promoting activity of benzodiazepine tranquilizers, diazepam and oxazepam, in mouse liver.

The widely used benzodiazepine tranquilizers diazepam and oxazepam promoted development of hepatocellular hyperplastic foci and hepatocellular neoplasms (adenomas and carcinomas) when they were fed in diet to male B6C3F1 mice after initiation by N-nitrosodiethylamine. Diazepam was more effective than oxazepam and its effect was proportionate to dose. Both diazepam and oxazepam induced hepatomegaly, cytochrome P-450 and cytochrome P-450-dependent aminopyrine N-demethylase activity in hepatocytes, effects similar to those produced by a well-known rodent liver tumor promoter, phenobarbital. In view of the importance and widespread use of this class of compounds, more work is warranted to examine their effects on tumor development in different mammalian species.

Aminopyrine N-Demethylase↗

PubMed1986

Final report of the Color Additive Scientific Review Panel.

The Color Additives Scientific Review Panel considered whether there was information sufficient to perform a carcinogenic risk assessment on the colors D&C Red No. 19 (R-19), D&C Red No. 37 (R-37), D&C Orange No. 17 (O-17), D&C Red No. 9 (R-9), D&C Red No. 8 (R-8) and FD&C Red No. 3 (R-3) and to evaluate the assessments sent to FDA as part of the petitions for use of the colors for drug and external uses by the Cosmetic, Toiletry and Fragrance Association (CTFA). There is a lack of human data concerning the colors for making a human health assessment, so the assessments are based upon the extrapolation of animal data. The risk assessments are determined for exposure to single chemicals. Excluded from consideration are possible effects from exposure to multiple chemicals, such as co-carcinogenesis, promotion, synergism, antagonism, etc. In the light of recent efforts in establishing a consensus in risk assessment, the Panel has determined that the CTFA assessments for R-10, O-17, and R-9 are consistent with present acceptable usages, although it questions some of the assumptions used in the assessments. The Panel identified a number of general assumptions made, and discusses their validity, their impact on total uncertainty, and the potential options to address the gaps in understanding that necessitate the assumption. The Panel also derived revised risk estimates using more "reasonable" assumptions than "worst-case" situations, for 90th percentile and average exposure. For those assumptions that are easily quantifiable, the Panel's estimates are less than an order of magnitude lower than the CTFA risk estimates, indicating that the underestimates and overestimates of the CTFA risk estimates tend to balance each other. The impact of most of the assumptions is not quantifiable. The assessment for R-3 is complicated by the fact that there is no good skin penetrance study for this color. It was assumed that the penetrance is similar to that of another water-soluble xanthene color, R-19. It is expected that the absorption of the color is not likely to exceed that of the smaller molecule, R-19. Therefore, the risk estimates are similar to the CTFA estimates, but with different reasoning. The estimates for R-8 and R-37 are different from the others in that there is a lack of any exposure or toxicological information on these colors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1986

Tumor-initiating and promoting activities of di(2-ethylhexyl) phthalate in vivo and in vitro.

The carcinogenic effects of di(2-ethylhexyl) phthalate (DEHP), including its potential as an initiator and as a promoter of carcinogenesis, were studied in mouse liver and skin and in rat liver in vivo, and in mouse epidermis-derived JB6 cells in vitro. A mouse model for liver initiation and promotion involved initiation by injection of N-nitrosodiethylamine (DEN) intraperitoneally into male B6C3F1 mice at 4 weeks of age, followed by exposure to either DEHP in the diet (3000, 6000, or 12,000 ppm) or phenobarbital in the drinking water (500 ppm), beginning 1 to 2 weeks later and continuing for periods of from 1 day to 18 months. Female F344/NCr rats were subjected to a similar protocol in which promotion continued for 14 weeks. DEHP promoted focal hepatocellular proliferative lesions (FHPL), including hyperplastic foci and neoplasms initiated by DEN in mice but not in rats. Skin-painting studies in female CD-1 or SENCAR mice involved initiation by a single topical exposure to 7,12-dimethylbenz[a]-anthracene (DMBA) applied to the dorsal skin, followed by repeated percutaneous exposure to a tumor promoter, either DEHP or 12-O-tetradecanoylphorbol-13-acetate (TPA). To test for two-stage skin tumor promotion, SENCAR mice were initiated with DMBA and then TPA was administered for only 2 weeks, after which DEHP was subsequently administered for 26 weeks. DEHP displayed very weak complete promoting activity and definite second stage promoting activity in SENCAR mouse skin, but was inactive under our conditions on CD-1 mouse skin. In vitro promoting activity of DEHP and its hydrolysis products, mono(2-ethylhexyl) phthalate (MEHP) and 2-ethylhexanol (EH), was studied by using promotable mouse epidermis-derived JB6 cells. DEHP and MEHP promoted JB6 cells to anchorage independence, while EH did not.

Adenoma↗

PubMed1986

Differential carcinogenic effects of intraperitoneal initiation with 7,12-dimethylbenz(a)anthracene or urethane and topical promotion with 12-O-tetradecanoylphorbol-13-acetate in skin and internal tissues of female SENCAR and BALB/c mice.

Groups of female SENCAR or BALB/c mice were initiated once intraperitoneally with 300 micrograms/mouse of 7,12-dimethylbenz(a)anthracene (DMBA) or 20 mg/mouse of urethane at 7 weeks of age. Beginning one week later, mice received topically applied acetone or 12-O-tetradecanoylphorbol-13-acetate (TPA), once weekly, at 2.5 micrograms/mouse for weeks 1 through 6 and 1.25 micrograms/mouse for weeks 7 through 52. The skin lesions were evaluated clinically. A complete necropsy was performed on all mice at week 52. SENCAR mice exposed to DMBA/TPA and urethane/TPA had more skin tumors than SENCAR mice exposed to DMBA or urethane alone and more than BALB/c mice in any treatment group. Of all skin carcinomas diagnosed histologically in DMBA/TPA-exposed mice, less than one-third had been identified clinically while the mice were alive. Most of the carcinomas arose within papillomas. BALB/c mice developed more vascular and uterine tumors than did SENCAR mice injected with DMBA and more lung and vascular tumors than did SENCAR mice injected with urethane. TPA exposure after treatment with either initiator had no significant effect on internal tumor development in either SENCAR or BALB/c mice.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1986

Pathology of aging female SENCAR mice used as controls in skin two-stage carcinogenesis studies.

The pathology of 60 aged female SENCAR mice used as acetone controls in skin painting studies was studied. Fifty percent of the mice survived past 96 weeks of age. The major contributing causes of death identified in 42 mice were glomerulonephritis (8 mice), histiocytic sarcoma (7 mice), and other tumors (8 mice). Glomerulonephritis was found in the majority of mice and was associated with thymic hyperplasia, focal vasculitis, and lymphoid hyperplasia. Necropsy of 58 mice surviving past 50 weeks of age revealed that 41 had an average of 1.36 tumors per mouse. The most common tumors included histiocytic sarcoma (13 mice), pulmonary adenoma or adenocarcinoma (11 mice), mammary tumors (11 mice), follicular center cell lymphoma (4 mice), and hepatocellular adenoma (4 mice). The 13 histiocytic sarcomas appeared to arise in the uterus and metastasized to liver (9 mice), lung (4 mice), kidney (3 mice), and other tissues. Lung tumors were of the solid and papillary types, and tumor cells frequently contained surfactant apoprotein (SAP) but did not contain Clara cell antigens, suggesting their origin from alveolar Type II cells. A variety of nonneoplastic lesions, similar to those observed in other mouse strains, were seen in other tissues of these mice. Amyloid-like material was seen only in nasal turbinates and thyroid gland. In a group of 28 mice exposed to 12-O-tetradecanoylphorbol-13-acetate (TPA) for up to 88 weeks, as a control for other treatment groups, 7 (25%) had papillomas and 5 (17.8%) had squamous cell carcinomas of the skin at necropsy, although many other induced papillomas regressed during the study.

Acetone↗

PubMed1986

Leu 7 immunoreactivity in fetal olfactory epithelium and dysplastic or neoplastic olfactory lesions induced in Syrian golden hamsters by N-nitrosodiethylamine.

The biotinylated monoclonal IgM antibody, anti-Leu 7 (HNK-1) was used to localize, by 2-step avidin-biotin immunocytochemistry, an antigen that appears in olfactory nasal epithelium of male Syrian Golden hamsters during N-nitrosodiethylamine (DEN) carcinogenesis. In normal young adult and adult hamsters, Leu 7 was not immunoreactive with nasal olfactory epithelium. In hamsters that had been given multiple doses of DEN, Leu 7 immunoreactivity was found throughout the olfactory epithelium. The carcinogen produced dysplastic and hyperplastic lesions in the olfactory epithelium as well as carcinoma in situ and poorly differentiated carcinomas, occasionally with rosette-like structures, all of which were immunoreactive with the Leu 7 monoclonal antibody. Other preneoplastic lesions and tumors (adenomas of nasal glands, papillomas, adenocarcinomas) in olfactory and respiratory nasal epithelium were never immunoreactive. Hamster fetuses expressed Leu 7 diffusely on olfactory epithelial cell membranes, neonatal hamsters had much less antigen, and 14- and 28-day-old hamsters contained few immunoreactive cells. Thus, evidence was provided that Leu 7 reacts with a fetal olfactory antigen which reappears during stages of chemically induced nasal carcinogenesis in Syrian Golden hamsters.

Animals↗

PubMed1986

Modifying effects of butylated hydroxyanisole, di(2-ethylhexyl)phthalate or indomethacin on mouse hepatocarcinogenesis initiated by N-nitrosodiethylamine.

Preneoplastic and neoplastic liver and lung lesions were studied in male B6C3F1 mice given a single injection (80 mg/kg) of N-nitrosodiethylamine (DEN) intraperitoneally at 4 weeks of age, followed 1 week later by oral exposure to di(2-ethylhexyl)-phthalate (DEHP; at 6000 ppm in the diet), butylated hydroxyanisole (BHA; 7500 ppm in the diet) or indomethacin (10 ppm in the drinking water) alone or in combination (DEHP and BHA or DEHP and indomethacin), and continued for 29 weeks. DEHP or BHA alone and the combination of DEHP and BHA increased the incidence of DEN-initiated focal hepatocellular proliferative lesions (FHPL), including both microscopic hyperplastic foci and hepatocellular adenomas. Mice that received BHA alone or DEHP plus BHA had FHPL that were composed predominantly of eosinophilic hepatocytes, while FHPL in DEHP-exposed mice were basophilic. Indomethacin showed neither promotional or antipromotional effects, except for lung tumors. Mice receiving DEHP and indomethacin after DEN had significantly fewer lung lesions. A high incidence of renal papillary necrosis and nephropathy was observed in the indomethacin-DEHP exposed mice, while these lesions were not found in mice treated with indomethacin alone or DEHP alone. These findings suggest that BHA, an antioxidant, promoted pre-neoplastic liver lesions while indomethacin, a known inhibitor of prostaglandin synthesis and a chemopreventive agent for colon and mammary tumors in other studies, had no effect on liver tumor promotion by DEHP.

Adenoma↗

PubMed1986

Dietary iodine deficiency as a tumor promoter and carcinogen in male F344/NCr rats.

Groups of 6-wk-old male F344/NCr rats received a single i.v. injection of either vehicle or N-nitrosomethylurea (Cas: 684-93-5) (MNU) at a dose of 41.2 mg/kg body weight. Two wk later, groups of rats were placed on iodine-deficient, iodine-adequate, or commercial (Wayne Lab Blox) diets, or one of these diets and without previous MNU injection. Animals were sacrificed at either 52 or 77 wk, or when they became moribund. Carcinogen-treated rats on the iodine-deficient diet for up to 52 wk had significantly increased thyroid gland weights and increased incidences of both thyroid follicular cell carcinoma (90%) and diffuse pituitary thyrotroph hyperplasia (90%) at 52 wk. The majority of the follicular carcinomas were transplantable and invasive into the mammary fat pad of weanling F344/NCr rats. No other tumors induced by MNU were affected by the iodine-deficient diets. Rats fed the iodine-deficient diet without MNU injection had a 40% incidence of thyroid follicular adenomas at 52 wk and 60% at 77 wk, and a 10% incidence of follicular carcinomas at 77 wk. Thus this experiment provided evidence that the iodine-deficient diet is a potent promoter of thyroid tumors initiated by MNU and carcinogenic by itself. In addition, pituitary tumors were found in 29 of the 58 rats treated with the carcinogen alone, compared to only 3 of the 20 rats in the control groups. The vast majority of these pituitary tumors contained prolactin that was demonstrable by the avidin:biotin:peroxidase complex immunocytochemical technique.

Animals↗

PubMed1985

Nucleotide sequences encoding and promoting expression of three antibiotic resistance genes indigenous to Streptomyces.

Promoter-probe plasmid vectors were used to isolate putative promoter-containing DNA fragments of three Streptomyces antibiotic resistance genes, the rRNA methylase (tsr) gene of S. azureus, the aminoglycoside phosphotransferase (aph) gene of S. fradiae, and the viomycin phosphotransferase (vph) gene of S. vinaceus. DNA sequence analysis was carried out for all three of the fragments and for the protein-coding regions of the tsr and vph genes. No sequences resembling typical E. coli promoters or Bacillus vegetatively-expressed promoters were identified. Furthermore, none of the three DNA fragments found to be transcriptionally active in Streptomyces could initiate transcription when introduced into E. coli. An extremely biased codon usage pattern that reflects the high G + C composition of Streptomyces DNA was observed for the protein-coding regions of the tsr and vph genes, and of the previously sequenced aph gene. This pattern enabled delineation of the protein-coding region and identification of the coding strand of the genes.

Base Sequence↗

PubMed1985

Effects of short-term exposure to the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate on skin carcinogenesis in SENCAR mice.

Skin tumor promotion after a short-term exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA) was studied in female SENCAR mice. Mice were dosed once by the topical application of 20 micrograms of dimethylbenz[a]anthracene (DMBA) in 0.2 ml acetone. A week later, they received topical applications of TPA (2 or 4 micrograms per 0.2 ml acetone) once or twice a week for periods of 1-10 weeks and were killed at 30 weeks. Skin tumors were counted and measured for size weekly. When TPA was applied once a week for 10 weeks or only twice a week for 2 weeks, there was significant promotion of papilloma formation in a large proportion of mice initiated with DMBA. Mice that received one or two applications had a few skin tumors. The total number of papillomas decreased considerably and the majority appeared to regress after 20 weeks in mice that received TPA treatment for 10 weeks. In mice that received only 4 TPA treatments, however, the majority of the papillomas grew progressively in size and did not regress during the entire experimental period. A greater proportion of these tumors progressed to carcinoma than did those in mice receiving TPA for 10 weeks. Thus, a short-term exposure was effective in causing certain changes in skin of SENCAR mice that led to tumor development and progression.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1985

Cloning and analysis of the promoter region of the erythromycin resistance gene (ermE) of Streptomyces erythraeus.

A DNA fragment containing the coding and regulatory sequences of the erythromycin (Er) resistance (ermE) gene of the Er produces Streptomyces erythraeus was cloned in Streptomyces lividans using the plasmid vector pIJ61. The approximate location and orientation of ermE were deduced from studies of its expression after subcloning in Escherichia coli. Sequences responsible for transcription of ermE in Streptomyces were studied by nucleotide (nt) sequencing, high resolution S1 and exonuclease VII mapping, in vitro transcription and in vivo promoter-probing. Tandemly arranged promoters of typical prokaryotic appearance initiate transcription of the coding region of ermE; a promoter of similar sequence was identified that initiates transcription of a likely coding region running in the opposite direction to ermE. It is suggested that these sites represent a class of vegetatively expressed Streptomyces promoter that is utilised by a form of RNA polymerase holoenzyme that also recognizes typical promoters of other bacterial genera.

Base Sequence↗

PubMed1985

Tumor-promoting effects of di(2-ethylhexyl)phthalate in JB6 mouse epidermal cells and mouse skin.

Di(2-ethylhexyl)phthalate (DEHP), a confirmed promoter of hepatocellular carcinogenesis in mice, was studied for tumor-promoting activity on the skin of SENCAR mice in vivo and on JB6 mouse epidermal cells in vitro. DEHP enhanced transformation to anchorage-independent growth of promotable JB6 clonal lines, C141, C121, and R219. DEHP induced colony formation in concentrations from 500 p.p.m. to 20 000 p.p.m./ml culture medium with maximum induction occurring at 10 000 p.p.m./ml. DEHP was inactive as a complete promoter of skin carcinogenesis initiated by 7,12-dimethylbenz[a]anthracene (DMBA) in SENCAR mice. Like the plant-derived natural product mezerein, however, DEHP significantly enhanced skin carcinogenesis in SENCAR mice when initiation by DMBA was followed by short term applications (2x/week, 2 weeks) of 12-O-tetradecanoylphorbol-13-acetate prior to application of DEHP. A random sample of the tumors observed was processed and examined histologically. Most neoplasms were papillomas; a few were squamous cell carcinomas. The kinds of tumors seen were identical with those reported in two-stage carcinogenesis experiments in SENCAR mice in which phorbol ester tumor promoters have been employed. Thus, DEHP promotes transformation in JB6 mouse epidermal cells and acts as a second-stage promoter in mouse skin carcinogenesis. DEHP therefore has promoting capability for at least two distinct kinds of epithelium in mice.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1985

Evidence for lack of promotion of the growth of the common naturally occurring basophilic focal hepatocellular proliferative lesions in aged F344/NCr rats by phenobarbital.

Aged female F344/NCr rats were exposed to phenobarbital (PB), 500 p.p.m. in the drinking water, from 26 months of age, for periods of 4, 8 or 9-27 weeks. In groups of control and PB-exposed rats sacrificed at these time periods the number and volume of basophilic and eosinophilic focal hepatocellular proliferative lesions (FHPL), including altered foci and adenomas in hematoxylin- and eosin-stained sections and FHPL identified histochemically by their content of gamma-glutamyl transpeptidase (GGT), were determined using computerized image analysis. Tritiated thymidine [3H]TdR was injected prior to sacrifice to determine labeling indices (LI) of normal hepatocytes and hepatocytes in FHPL. Rats receiving PB had significantly increased numbers and volumes of eosinophilic and GGT-positive FHPL while the numbers and volumes of the common basophilic FHPL seen in controls were not affected by PB exposure. The LI of all FHPL were higher than that of normal hepatocytes, but PB exposure did not affect the LI of basophilic FHPL. An uncommon GGT-positive FHPL found in control rats was detected in zone 1 of the hepatic acinus, a similar location of the GGT-positive eosinophilic FHPL seen in PB-exposed rats, while the common basophilic FHPL was observed in zones 1-3. These findings suggest that PB does not promote the growth or development of the common naturally occurring basophilic FHPL but either promotes the uncommon GGT-positive FHPL or induces new FHPL de novo.

Adenoma↗

PubMed1985

Secretory proteins of the lung in rodents: immunocytochemistry.

The reactivity of rabbit antisera to rat lung secretory proteins with other rodent species was evaluated by immunocytochemistry. Rabbit anti-rat surfactant apoprotein antiserum reacts with the cytoplasm of rat, mouse, and hamster type II pneumocytes and is specific for these cells. Rabbit antiserum to rat Clara cell secretory proteins stains rat, mouse, and hamster Clara cells. Rabbit antisera specific to the two antigenic types of rat Clara cell antigens were also both reactive with rat, mouse, and hamster Clara cells. An antiserum to the non-serum proteins of hamster lung lavage was also prepared and shown to be specifically reactive with hamster Clara cells. The availability of specific reagents for secretory proteins of rodent lungs is expected to facilitate studies of the respective cell types in various pathologic states.

Animals↗