PubMed Health⌕ Search

Biomedical subjects

P J Tofilon

Publications and source records attributed to P J Tofilon.

80 records · Page 5Linked to original sources
PubMed1981

Effect of folate deficiency on microsomal drug metabolism and heme content in the intestinal mucosa of guinea pigs.

The relationship between folate deficiency, heme content, and microsomal drug metabolism in the intestinal mucosa of the guinea pig was examined. Weanling male guinea pigs were pair-fed a folate-deficient diet, and intestinal mucosal folate levels were measured. A significant decrease (75%) in these levels was observed at 3 weeks after diet initiation. A significant decrease (78%) in intestinal mucosal drug metabolism (7-ethoxycoumarin O-deethylase activity) and a significant decrease (46%) in intestinal mucosal heme content were also observed at this time. These findings indicate that folic acid deficiency in the guinea pig results in a marked reduction in heme content and microsomal drug metabolism of the intestinal mucosa.

Animals↗
PubMedDate not supplied

Antitumor and antimetastatic activity of the differentiating agent N-methylformamide in murine tumor systems.

N-Methylformamide (NMF), a cell-differentiating agent, was assessed for its antitumor activity against a fibrosarcoma (FSA), a hepatocarcinoma (HCA-I) and a mammary carcinoma (MCA-K), syngeneic to C3Hf/Kam mice. Tumors were grown as solitary tumors in the leg or as artificial or spontaneous micrometastases in the lung. NMF, at a dose of 300 mg/kg, was administered i.p. daily for 6 to 18 days. NMF slowed the growth of FSA and HCA-I tumors and totally inhibited the growth of the MCA-K tumor. However, the effect was transient; tumors resumed their pretreatment growth rate upon cessation of the treatment. Histologically, MCA-K tumors treated with NMF (300 mg/kg daily for six days) underwent considerable cell depopulation and reduction in mitotic activity. The number of artificial metastases, as well as the incidence and the number of spontaneous metastases, were markedly reduced by NMF. This resulted in a prolongation of the survival of mice that had artificial metastases of MCA-K tumor. The in vitro clonogenicity of MCA-K, but not of FSA or HCA-I cells, was reduced. However, in vivo reduction of MCA-K cell clonogenicity was minimal, if any. Thus, NMF is effective in restricting the growth of both solitary tumors and metastases, but the degree of response is highly dependent on tumor type.

Animals↗
PubMedDate not supplied

Enhancement of in vitro chemotherapeutic activity by dimethylsulfoxide.

The effects of the differentiation-inducing polar solvent dimethylsulfoxide (DMSO) on the in vitro response of murine hepatocarcinoma cells to cisplatinum, BCNU, and melphalan were investigated using the sister chromatid exchange (SCE) and cell survival assays. Growth of cells in medium containing 2 per cent DMSO enhanced drug-induced SCEs and cell kill. In order for the enhancement to occur, cells had to be exposed to DMSO for at least 48 h prior to drug treatment. The presence of DMSO during drug treatment did not affect cell response to the three chemotherapeutic agents. The enhancement of chemosensitivity was eliminated within 24 h of DMSO removal. These data suggest that the differentiation-inducing polar solvents may provide antineoplastic benefits when administered in combination with standard chemotherapeutic agents.

Animals↗
PubMedDate not supplied

Microglial cytokine gene induction after irradiation is affected by morphologic differentiation.

Microglia are known to play an important role in the CNS cytokine network, and their response after irradiation may be associated with the development of radiation-induced tissue damage. Radiation effects on this cytokine network have not yet been elucidated. We investigated the effect of gamma-irradiation on microglia stimulated with Zymosan A and lipopolysaccharide (LPS), which alone induce the expression of some cytokines and neurotoxic products by microglial cells. In the resting condition (ramified microglia), radiation had no effect on the mRNA level corresponding to cytokines such as IL1beta or IL-6, although TGF-beta1 mRNA was minimally enhanced by irradiation. However, in the activated microglia (amoeboid microglia) stimulated with Zymosan A, radiation-induced IL-6 mRNA expression was increased about two-fold in comparison with non-irradiation. IL-1beta was slightly induced by 2 Gy irradiation, but was not induced by higher doses. TGF-beta1 mRNA was not enhanced by radiation following Zymosan stimulation. In the LPS-stimulated condition, IL-6 mRNA was induced only by 2 Gy of irradiation, but no change in the expression of other genes was detected. These results suggested that radiation exerted different effects on cytokine gene transcription in microglia depending on their morphological state.

Animals↗