Showing papers on "Intraperitoneal injection published in 1981"

Effect of indomethacin on intestinal tumors induced in rats by the acetate derivative of dimethylnitrosamine

Abstract: Over the course of 20 weeks, Sprague-Dawley rats developed intestinal tumors in response to an intraperitoneal injection of the acetate derivative of dimethylnitrosamine. The same agent did not induce tumors in Lobund-Wistar rats. The number of tumors was significantly smaller in rats given drinking water containing indomethacin (beginning 14 days after the injections) than in control rats given drug-free water.

Use of monoclonal antibody directed against herpes simplex virus glycoproteins to protect mice against acute virus-induced neurological disease.

Abstract: Monoclonal antibodies HCl and HD1, directed against herpes simplex virus type 1 (HSV-1) glycoproteins gC and gD, respectively, were evaluated for their ability to passively immunize mice against acute virus-induced neurological disease after footpad inoculation with HSV-1 or herpes simplex virus type 2 (HSV-2). Control virus-infected mice receiving a single intraperitoneal injection of normal serum died within 7 to 10 days after the spread of virus from footpad to spinal cord and brain. However, a single intraperitoneal injection of either HCl or HD1 antibody protected mice from neurological illness and death when administered to HSV-1 (strain HTZ)-infected mice at either 2 h before virus challenge or at 24 h after virus inoculation. To determine the in vivo specificity of the antibodies, passive transfer studies were performed with mice infected with the MP strain of HSV-1, a mutant of HSV-1 (mP) which is defective in the production of glycoprotein gC. Whereas HD1 antibody decreased the incidence of neurological illness in MP- and mP-infected mice, HCl antibody, which protected mP-infected animals, failed to protect mice infected with the MP strain. When HD1 antibody was administered to HSV-2 (strain G)-infected mice at either 2 h before virus challenge or at 6 h (but not 24 h) after virus inoculation, 100% of the infected animals receiving HD1 antibody survived. In contrast, 100% of HSV-2 (strain G)-infected animals passively immunized with HCl antibody developed neurological illness and died. These results provide in vivo evidence that the HSV-induced glycoprotein gC expresses type-specific antigenic determinants, whereas glycoprotein gD expresses type-common determinants.

Fetal exposure to ethanol enhances pituitary-adrenal and temperature responses to ethanol in adult rats.

Abstract: Long lasting effects of perinatal ethanol exposure were studied in adult rats who were the offspring of dams fed a 5.0% w/v ethanol-containing liquid diet ad libitum or pair-fed the isocaloric control diet during gestation weeks 2 and 3 or during postnatal week 1. Fetal exposure to ethanol reduced body weight of pups at birth unless the ethanol diet was supplemented with casein; neonatal exposure to the ethanol or pair-fed diets, casein supplemented or not, reduced pup weights until day 21 postnatally when weights of all fetally or neonatally exposed pups were normal. Between 52 and 120 days of age females were tested for pituitary-adrenal and temperature responses to a challenge dose of ethanol. Prenatally ethanol-exposed rats showed significantly higher plasma corticosterone titers and developed a greater hypothermia in response to an intraperitoneal injection of ethanol (0.75--1.5 g/kg) than did pair-fed controls. Similar responses enhancement did not occur in the postnatally ethanol-exposed rats. Temporal patterns of blood ethanol levels after an intraperitoneal injection of ethanol (1.5 g/kg) were similar in prenatally ethanol-exposed females and their pair-fed controls. The data indicate that exposure to ethanol in utero exerts persistent effects on the offspring, rendering them more responsive to the hypothermic and pituitary-adrenal activating effects of alcohol as adults.

Early appearance of histochemically altered hepatocyte foci and liver tumors in female rats treated with carcinogens one day after birth

Abstract: A single i.p. injection of diethylnitrosamine (DEN) or benzo(a)pyrene (BAP) in 1-day-old female rats produced a high incidence of ..gamma..-glutamyltranspeptidase-(GGT)- positive hepatocyte foci within 4 weeks after the rats were weaned onto a 0.05% phenobarbital diet; the injection of benzo(e)pyrene did not produce foci under these conditions. Liver tumors appeared in rats treated with DEN within 8 weeks after weaning and in BAP-treated rats within 16 weeks after weaning. The results suggest that the treatment protocol used in this study may increase the utility of the liver tumorigenesis model as a broadly applicable in vitro system for the rapid detection of tumorigenic potential in environmental contaminants.

Edema and hemoconcentration in mice experimentally infected with Vibrio vulnificus.

Abstract: Vibrio vulnificus (lactose-positive Vibrio), a recently recognized pathogenic marine species, produced extreme hemoconcentration and death within 3 to 6 h after subcutaneous or intraperitoneal injection of 10(8) viable cells into mice; hemotocrit values approached 70% (normal, 45%). About 1 ml of edema fluid accumulated at the site of each subcutaneous injection, and locally increased vascular permeability was demonstrated by a skin bluing assay, using Evans blue dye. A corresponding fluid accumulation did not occur in the peritoneal cavity after an intraperitoneal injection. Filter-sterilized supernatants of cultures grown under a variety of conditions did not produce local edema or lethality, nor did whole Vibrio cells killed by a variety of methods or disrupted by sonic oscillation. Edema fluids collected from infected mice and sterilized by filtration had no effect when they were injected subcutaneously or intraperitoneally into mice. Inocula of 10(9) viable cells of V. vulnificus contained within a diffusion chamber implanted subcutaneously did not produce skin bluing, edema, or lethality; Vibrio cells remained viable and virulent within these chambers for at least 2 weeks. These experiments suggested that vascular permeability changes in V. vulnificus infections may not be attributable to a diffusible toxin and may require direct contact between host cells and viable Vibrio cells.

Functional and structural rat kidney changes caused by peroral or parenteral lithium treatment.

Abstract: Renal functional and structural changes were studied in rats treated with lithium for 5 months. The lithium was administered in two different ways: in the food or as a daily intraperitoneal injection. In the perorally treated rats serum lithium was relatively constant during the day. In the injected rats serum lithium reached a high peak value just after the injection followed by a decrease to very low values. In all rats an increased water consumption and a reduced renal concentration ability were seen during lithium treatment. Light microscopy showed focal degenerative changes in the distal convoluted tubule and collecting ducts. These changes comprised nuclear and cellular polymorphism and tubular dilatation. The functional as well as the structural changes were most pronounced in the rats treated with peroral lithium, and a correlation between the functional and morphological changes was present. It is concluded that lithium is more harmful to the kidney when the administrations give a relatively constant serum lithium level, such as in peroral administration, than when administration causes great variations, including peak values and very low minimum levels in serum lithium. The reason for this might be that a number of regenerative processes occur only in periods with low lithium concentrations.

Cytotoxic T cells in small intestine epithelial, lamina propria and lung lymphocytes.

Abstract: We have examined the development of specific cytotoxic T-cell activity in the lungs and the epithelium and lamina propria of the small intestine following tumour cell inoculation by subcutaneous or intraperitoneal routes. After an intraperitoneal injection of tumour cells, large amounts of cytotoxic activity are detectable in the lungs and lamina propria. In comparison, the epithelial lymphocytes of the small intestine display low cytotoxic activity. After a subcutaneous injection, little cytotoxicity is detectable except in the lungs and the development of such cytotoxicity has a much shorter time course compared with that induced by an intraperitoneal inoculation of tumour cells. The data indicate a marked difference in the functional capacity of lymphocytes from the epithelium and lamina propria of the small intestine.

Alterations of Inositol Lipid Metabolism of Rat Sciatic Nerve in Streptozotocin‐Induced Diabetes

Abstract: The composition and metabolism of rat sciatic nerve phospholipids were studied 20 weeks after induction of chronic diabetes by intraperitoneal injection of streptozotocin (50 mg/kg). On a wet weight basis the nerves from the diabetic animals showed a 7% decrease in total phospholipid from that of controls and a relative decrease in phosphatidylinositol. Incubations of isolated sciatic nerves of diabetic rats in a medium containing [33P]orthophosphate gave decreased labeling of phosphatidylinositol and substantial changes in the labeling pattern of phosphatidylinositol phosphate and 4,5-bisphosphate from that of controls. The ratio of label in these polyphosphoinositides decreased from 2.5 for normal nerve to about 1.0 for diabetic nerve within a 2-h incubation period. These metabolic alterations were not observed in acutely diabetic animals 5 days after streptozotocin (100 mg/kg) administration. Because polyphosphoinositides may be involved in the control of membrane permeability during axonal conduction, alterations in their relative amounts or turnover rates could be related to the physiological changes of early diabetic neuropathy.

Teratogenic effects of aliphatic nitriles.

Abstract: Intraperitoneal injection of acrylonitrile at 1.51-2.26 mmole/kg (80-120 mg/kg) or propionitrile at 0.54-1.51 mmole/kg (30-83 mg/kg) on the morning of Day 8 of gestation in the hamster induced exencephaly, encephalocoeles, and rib fusions and bifurcations in the offspring. These doses of the aliphatic nitriles also resulted in obvious toxicity to the dams. Multiple intraperitoneal injections of sodium thiosulfate at 4.03 mmole/kg (1 gm/kg) protected both dams and embryos against toxicity. When the larger doses of either acrylonitrile or propionitrile were given in the presence of sodium thiosulfate, teratogenic effects were observed in the absence of overt signs of maternal poisoning. A survey of the literature describes many studies which demonstrate that acrylonitrile and propionitrile are converted in vivo to toxicologically significant concentrations of cyanide and that sodium thiosulfate, an established cyanide antagonist, can provide protective actions against poisoning by either acrylonitrile or propionitrile. The observations suggest that the teratogenic effects of both acrylonitrile and propionitrile are related to the metabolic release of cyanide.

On the 48÷80-induced secretion of tissue mast cells and its mitogenic effect on nearby cells in the intact rat

Abstract: Histamine release from tissue-bound mast cells and cell proliferation in the proper mesentery in the intact rat was quantitated following in intraperitoneal injection of graded doses of compound 48/80. The dose-response curves were sigmoid-like in linear-log plots. ED50 for histamine release was 0.035-0.040 and for increased cell proliferation 0.040-0.048 microgram per g BW. The proliferative response following mast-cell secretion ceased after a period of between 48-72 h, irrespective of whether a high or a low dose of 48/80 was used. Basal on the net rate of histamine synthesis (ca. 0.45 microgram/g mesentery wet weight/h) after an initial injection of 48/80, on the extent of histamine release and the proliferative response after a repeated injection of 48/80, it is concluded that there is a lag period of at least 3 days before proliferation can be re-stimulated by renewed 48/80-induced mast-cell secretion.

Inhibition of pulmonary metastasis of Lewis lung carcinoma by a glucan, Schizophyllan.

Abstract: The effect of a glucan, Schizophyllan (SPG), on pulmonary metastases in syngeneic mice bearing Lewis lung carcinoma (3LL) was examined. As a model of pulmonary metastases, 3LL cells were implanted into the footpads of C57BL/6 mice, the resulting primary tumor was removed 9-10 days later. The inhibitory effect of SPG was evaluated from the number of pulmonary surface nodules on the lungs about 3 weeks after tumor implantation. SPG was found to have antimetastatic activity, which depended on its dose and time of injection. A single injection of 100 or 200 mg/kg or daily injections of 20 or 50 mg/kg of SPG after removal of the primary tumor markedly inhibited pulmonary metastases. Combined therapy with cyclophosphamide and SPG significantly prolonged the survival of mice with pulmonary metastases. Enhancement of the in vitro cytotoxic activity of peritoneal macrophages and bronchoalveolar or whole lung cells against 3LL cells was noted in SPG-treated mice on day 7 after a single intraperitoneal injection of 100 mg/kg SPG. Intravenous transfer of peritoneal macrophages activated with SPG inhibited the development of pulmonary micrometastases.

Dissociation of bactericidal activity from other functions of activated macrophages in exudates induced by thioglycolate medium.

Abstract: Macrophages displayed increased spreading, increased Fc-receptor-mediated phagocytosis, and increased secretion of plasminogen activator when collected from the peritoneal cavities of either Listeria-immune mice challenged intraperitoneally 3 days earlier with Listeria or nonimmune mice injected intraperitoneally 3 days earlier with fluid thioglycolate medium. In contrast, macrophages from the thioglycolate-induced peritoneal exudates were severely impaired in vitro in their ability to destroy Listeria. Injection of thioglycolate markedly interfered with the destruction of sublethal intraperitoneal challenge of Listeria, which resulted in nonimmune animals dying of an overwhelming systemic infection. In animals immune to Listeria, injection of thioglycolate delayed the onset of the expression of immunity to an intraperitoneal challenge of bacteria. The thioglycolate-induced suppression of bactericidal activity was determined to be confined to the site of injection. Results of experiments indicated that the colloidal agar in thioglycolate medium was the cause of the impairment of macrophage bactericidal activity. In addition to the impairment of bactericidal activity induced by agar, additional studies showed that an intraperitoneal injection of colloidal agar (0.075% wt/vol) by itself was a sufficient inflammatory stimulus for the accumulation of a large number of host phagocytic cells.

Effect of corticosterone and its route of administration on muscle protein breakdown, measured in vivo by urinary excretion of Nτ-methylhistidine in rats: Response to different levels of dietary protein and energy

Abstract: Adrenalectomized young male rats were given a large dose of corticosterone ( 10 mg 100 gm body weight ) either by subcutaneous or intraperitoneal injection. Subcutaneous injection caused immediate cessation of growth and an elevation in urea and in Nτ-methylhistidine (3-Mehis) output in the urine, the latter indicative of accelerated muscle protein breakdown. On the other hand, intraperitoneal administration resulted in only slight retardation of growth and no change in 3-Mehis output. Since the plasma level of corticosterone was more elevated by subcutaneous than by intraperitoneal administration of the hormone, it was concluded that direct passage of the intraperitoneal dose through the liver inactivated more of the administered hormone and thus prevented the level in the peripheral blood from rising to the critical concentration necessary to cause acceleration of muscle protein breakdown. This explains some reports in the literature of lack of action of corticosteroids on muscle protein breakdown. When corticosterone ( 10 mg 100 gm body weight ) was administered subcutaneously to young adrenalectomized rats receiving diets deficient in protein and/or energy, they lost weight at the same rate as did rats on an adequate diet. In addition, the gastrocnemius, tibialis, and extensor digitorum longus muscles lost weight and output of 3-Mehis was elevated irrespective of the diet. When a lower dose of corticosterone ( 0.8 mg 100 g body weight ) was given subcutaneously, the pattern of growth or weight loss on the different diets was not affected and the weights of the leg muscles relative to body weight remained unchanged. Output of 3-Mehis was slightly and transiently elevated for rats on the energy-deficient and protein-energy deficient diets receiving this low dose of corticosterone, but not for rats on the protein-deficient or adequate diets. Since the livers of the animals on the low energy intakes were smaller, we attribute the slight action of the lower corticosterone dose on 3-Mehis output to less efficient hepatic removal of the hormones. Thus, diet appears to modify the action of corticosteroids mainly through changes in the rate of hormone inactivation. It is concluded that dietary intake of protein and energy and corticosterone affect muscle protein turnover independently of one another.

Interaction Between Zinc Deprivation and Acute Ethanol Intoxication During Pregnancy in Rats

Abstract: A single intraperitoneal injection of ethanol given at gestational day 10 to pregnant rats undergoing transient zinc deprivation increases the prob ability of complications in the pregnancy, compared to either intoxication in well-fed dams or to zinc deprivation alone. The results suggest that dietary factors may contribute to ethanol-induced terata and that non-abusive or infre quent maternal use of ethanol can be particularly dangerous to the fetus during a dietary deficiency. J. Nutr. 111: 2034-2038, 1981.

Antitumor activity of mitomycin C-dextran conjugate against various murine tumors.

Abstract: The antitumor activity of a high molecular weight pro-drug of mitomycin C(MMC), MMC-dextran conjugate (MMC-D), was examined against various murine tumors under different experimental conditions A single intraperitoneal injection of MMC-D exhibited higher antitumor activity against intraperitoneally inoculated B16 melanoma, Ehrlich ascites carcinoma, and P388 leukemia than MMC, but lower activity against BDF1 mouse-transplanted L1210 leukemia Intratumoral injection of MMC-D showed a superior effect on subcutaneously implanted B16 melanoma, while intravenous injection of MMC-D exhibited reduced activity against P388 and L1210 leukemia compared with MMC Prior administration of MMC-D at 24 hr before tumor inoculation resulted in a significant increase of the life span of mice bearing L1210 leukemia, suggesting that it shows sustained pharmacological activity These differences between the activities of MMC-D and MMC in various tumor systems are considered to reflect the improved biopharmaceutical properties of MMC-D resulting from the modification of MMC into a polymeric drug

The tissue distribution of gold, copper and zinc in animals treated with Au (III); species differences in the binding of these metals in the kidney.

Abstract: Whole body retention of Au and the distribution of Au, Cu and Zn have been measured in female rats, rabbits, guinea-pigs, hamsters and mice after either a single injection or multiple doses of Au(III). At 24 h after a single intraperitoneal injection whole body retention of Au was about 65% of the dose in the rabbit and 50% of the dose in other species. After five doses, retention (as a percentage of the total dose) ranged from 36% in mice to 49% in rats. Concentrations of Au in the kidneys were lowest in mice and highest in rats but, in all species, were greater than in other organs. In rats and guinea-pigs, but not in hamsters, rabbits and mice, treatment with Au(III) increased the Cu content of the kidneys and of the soluble fraction isolated therefrom. The latter from the rat and guinea-pig kidney contained both Au and Cu in association with a low molecular weight metalloprotein (metallothionein), which also contained Zn and was separated by ion exchange chromatography into three subspecies. Binding of Au by these metalloproteins appeared to be related to the renal accumulation of Cu. Apart from the mouse, in which renal accumulation of Au was low, slight damage resulted in the kidneys of all species after treatment with Au. It appears, therefore, that nephrotoxicity cannot be explained simply by the renal concentration of Au and the form in which it is accumulated within the tubular cells.

Age-dependent mitogenesis in normal connective tissue cells

Abstract: We have previously described ways to use the mesentery for studies of proliferation in intact tissue. Here we have studied a weak and a strong mitogenic response in the mesentery of rats aged 6-42 weeks, induced by a single intraperitoneal injection of saline or the mast-cell-degranulating drug 48/80. Proliferation was measured by the specific DNA activity, the fraction of fibroblast- and mesothelial-like cells in the S + G2 cell-cyclephases, and the mitotic index. We also counted the relative number of mast cells in the tissue (normalized to 5,000 fibroblast-like and mesotheliallike cells), since this might influence 48/80-induced mast-cell-mediated proliferation.

Gastrointestinal ulceration in the guinea pig in response to dimaprit, histamine, and H1- and H2-blocking agents.

Abstract: Histamine is known to induce gastric ulcers in guinea pigs after intraperitoneal administration and duodenal ulcers after repeated intramuscular administrations. This study was undertaken to clarify further the differential role of H1 and H2 receptor sites in respect to gastric and duodenal ulcer in the guinea pig. Groups of guinea pigs were treated with histamine, intraperitoneal (1.81 mg/kg intraperitoneal) or intramuscular (0.09 mg/kg intramuscular×8 doses); the selective H2 agonist dimaprit (0.09–0.18 mg/kg×8 doses intramuscular or 1.81–3.62 mg/kg intraperitoneal); NaCl, 154 mM (control); and the selective H1 and H2 antagonists, diphenhydramine (125 mg/kg×2 doses, intramuscular) or cimetidine (50 mg/kg×3 doses, intramuscular). Gastric and duodenal lesions were evaluated and residual gastric contents were analyzed. The selective induction of gastric or duodenal ulceration by histamine was confirmed, and the H2 agonist, dimaprit, has been shown to be ulcerogenic to the guinea pig duodenum by intraperitoneal or intramuscular administration. Diphenhydramine produced considerably more protection against histamine-induced gastric ulceration (62% decrease in incidence), while cimetidine was particularly effective in the prevention of histamine-induced duodenal ulcer (64% decrease in incidence). A differential role of histamine in the pathogenesis of gastric as opposed to duodenal ulcer is suggested by the present findings.

Acute effects of phenytoin on peripheral nerve function in the rat.

Abstract: The acute effect of intraperitoneal injection of phenytoin on rat peripheral nerve was studied. Conduction velocities in the ventral caudal nerve were measured hourly and phenytoin blood levels were obtained 4 to 5 hours after injection. Conduction velocity decreased by 23% in the 25 phenytoin-treated animals from a control value of 30.0 plus or minus 1.3m/sec (mean plus or minus SEM) to a 4-hour value of 23.0 plus or minus 1.3 m/sec (P less than 0.001). The phenytoin blood level 4 hours after injection was 45.0 plus or minus 1.3 micrograms/ml. Amplitudes of evoked muscle action potentials in the treated group decreased by 37% from control values. High levels of phenytoin induce prompt slowing of nerve conduction velocity within hours, which may be mediated by mechanisms similar to those responsible for toxic central effects.

In Vivo and ex Vivo Effects of Copper on Rat Liver Metallothionein

Abstract: In order to test the hypothesis that exogenous copper could displace endogenous zinc from metallothionein under in vivo and ex vivo conditions, a series of zinc-copper competition experiments were conducted with rat liver. Intraperitoneal injection of zinc alone resulted in a large increase in zinc and a small increase in copper associated with hepatic metallothionein 24 hr later, as compared to controls. Intraperitoneal injection with copper alone resulted in increases in both zinc and copper bound to metallothionein 6 hr later. Intraperitoneal injection of zinc at time zero and copper at 18 hr, followed by killing at 24 hr, resulted in no increase in zinc, but a significant increase in copper, bound to metallothionein. Exposure of rat livers to copper ex vivo in an isolated perfusion apparatus gave different results from the in vivo experiments in regards to the metal composition of metallothionein. Animals were injected i.p. with zinc at time zero, and their livers were removed at 18 hr for a 2-hr perfusion. The zinc and copper contents of metallothionein in the groups receiving zinc in vivo and then either killed or perfused without additional metal were the same. The group which received zinc in vivo and copper exmore » vivo showed a large decrease in its metallothionein zinc content, a decrease which was matched almost exactly by a large increase in its metallothionein copper content. These results are consistent with the above-mentioned hypothesis and with recent in vitro results demonstrating the ability of copper to displace zinc from metallothionein.« less

Appearance of Fucolipid after Conventionalization of Germ-Free Mice

Abstract: Incorporation of [6-3H]fucose and [1-14C]glucosamine into the lipid fraction of microvillus membrane (MVM) was studied in germ-free and conventionalized mice after intraperitoneal injection of the radioactive precursors. Incorporation of [6-3H]fucose was clearly detected in conventionalized mice but not detectable in germ-free mice. There was no difference in the incorporation of [1-14C]glucosamine between the two groups. The lipid fraction of MVM labeled with [6-3H]fucose showed a spot of slower mobility than asialo GM1 on TLC with autoradiography and it was confirmed to be a fucolipid on abolishing the radiolabeled original spot by alpha-L-fucosidase treatment. These results suggest that the synthesis of the fucolipid is induced by conventionalization of germ-free mice.

Phagocytosis and killing of salmonella typhimurium by peritoneal exudate cells.

Abstract: Normal peritoneal cells from conventional, germfree, or nu/nu mice readily killed opsonized salmonellae, an observation that suggests that this activity in the normal peritoneal cavity may not be dependent on either environmental antigenic stimulation or T-cell mediation. In contrast, peritoneal cells elicited 4 days after injection with thioglycolate medium failed to kill opsonized salmonellae but appeared to be highly phagocytic. Peritoneal cells from thioglycolate-treated mice could be induced to kill opsonized salmonellae by giving the mice a primary footpad injection and a secondary intraperitoneal injection of Corynebacterium parvum. This activation by C. parvum appeared to be thymus dependent, since it did not occur in nu/nu mice.

Multicellular in vivo sister-chromatid exchanges induced by urethane.

Abstract: Following urethane inhalation exposure, clear dose—response relationships were apparent in all cell types examined in hepatectomized and intact mice. At concentrations of 0.1 mg/l and higher, induced SCE frequencies were linearly related to log urethane concentrations. No significant differences in SCE response between like cell types of hepatectomized and intact mice were apparent. In hepatectomized mice, there was no significant difference in the SCE response of regenerating liver and alveolar macrophage cells. However, bone-marrow response was significantly lower ( p = 0.01). Likewise, in intact mice bone marrow response was significantly lower than in alveolar macrophages ( p = 0.01). Inhalation and intravenous infusions of the same total dose of urethane (193 mg/kg) administered over a 4-h period produced comparable SCE responses in all cell types. However, a single intraperitoneal injection of 193 mg/kg just prior to BrdU infusion produced significantly higher SCE frequencies in bone marrow ( α = 0.01), and alveolar macrophages ( α = 0.05) of intact mice than did the equivalent inhalation dose. Intraperitoneal injections produced similar results in 2-month-old mice as in 4-month-old mice. However, regardless of the route of administration SCE frequencies in regenerating liver and/or alveolar macrophages were significantly higher than in bone marrow.