DNA is considered to be an important target for the antitumor and toxic properties of the Chloroethylnitrosoureas. Since the main target for their dose-limiting toxicity and the antileukemic efficacy is believed to be the bone marrow, we have compared the formation and subsequent removal of DNA-DNA interstrand cross-links in the bone marrow of rats which had received a single i.p. injection (10...

The susceptibility of hepatocytes to carcinogenesis in vivo may be influenced by the phase of the cell cycle at which carcinogen-induced damage is incurred. In order to better understand this relationship, hepatic cell proliferation in juvenile male Fischer 344 rats was charted following a two-thirds partial hepatectomy. For hepatocytes, two distinct waves of DNA synthesis occurred which were f...

Following implant of cotton thread-carrying 3-methyl-cholanthrene into the pancreas tissue of 90 C57BL/6 and 60 BALB/c mice, 13 developed ductal adenocarcinomas. Two of these tumors, both of C57BL/6 origin (Panc 02 and 03), were established in serial s.c. transplant. Panc 02 was treated with 37 different anticancer drugs representing all of the chemical and functional classes of clinically usef...

Various strains of mice demonstrate widely differing susceptibility to chemical induction of thymic lymphomas, in both timing and incidence. In AKR mice tumors appear very early and at high incidence after a single dose of W-methyl-jV-nitrosourea, while in other strains they appear later and at lower incidences. In an attempt to determine the potential role of AKR ecotropic murine leukemia viru...

The effects of single agent therapy with 1-(-chloroethyl)-3-cyclohexyl-1-nitrosourea, 5-fluorouracil, and 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide on a human malignant melanoma transplanted and passed serially in thymusless nude mouse were studied. Tumor response varied. A single dose of 1-(-chloroethyl)-3-cyclohexyl-1-nitrosourea induced initial tumor regression, but thereafter grow...

The s.c.-propagated murine glioma, GL-26, was established in tissue culture. The tissue culture line, with a doubling time of 36 hr, was used as the common source for all tumor cells. Suspensions of the tumor cells were transplanted intracerebrally in mice to produce an anaplastic ependymoblastoma. In vitro 51-Cr cytotoxicity assays did not detect any cellular immunity against GL-26 tumor cells...

The influence of the radiosensitizer misonidazole on the effectiveness of several alkylating agents and cis-platinum against advanced solid murine tumors was investigated. Tumor regrowth delay, frequency of tumor regressions, and animal life span were used to evaluate misonidazole in combination with cyclophosphamide, L-phenylalanine mustard, 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl)-1-nitr...

The heterotopic urinary bladder with a communicating reservoir is a potentially useful model for bladder carcinogenesis studies. As a test of whether such bladders will develop transitional cell carcinomas after chronic carcinogenic stimuli, two carcinogens, N-methyl-N-nitrosourea and N-butyl-N-(3-carboxypropyl)nitrosamine, were instilled repeatedly into the reservoir connected with the heterot...

The present study with N-methyl-N-nitrosourea and rat brain DNA was performed in order to study the distribution of alkylated products and the difference in the removal of these products from DNase I-sensitive and -resistant regions of DNA. Nuclei were isolated from N-[3H]methyl-N-nitrosourea-treated rats and incubated in the presence of DNase I (5 microgram/ml). Digested DNA was further hydrol...

Tocopherols are present in significant amounts in vegetable oils used in human foods. The most prevalent tocopherols in foods are the alpha, beta, gamma, and delta variants with (RRR) stereochemistry. Tocopherols are lipophilic phenolic antioxidants, produced by plants. In the United States, gamma-tocopherol is the most prominent dietary tocopherol due to its high amount in the dominant commerc...