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M L Cunningham

Publications and source records attributed to M L Cunningham.

102 records · Page 6Linked to original sources
PubMed1985

Superoxide anion is generated from cellular metabolites by solar radiation and its components.

Several endogenous cellular constituents were tested for their ability to produce superoxide anion (O2-) from ground-state molecular oxygen upon irradiation by solar radiation. The pyridine cofactors NADPH and NADH, riboflavin, and the nucleosides 2-thiouracil and 4-thiouridine were found to sensitize the transmission of photon energy from solar radiation and monochromatic radiation (290, 334, 365, and 405 nm) to oxygen, resulting in O2- formation, as detected by superoxide dismutase-inhibitable cytochrome c reduction. Quantum yields for the production of O2- indicate that NADPH is the most efficient and riboflavin the least efficient of the compounds tested. These data indicate that endogenous compounds may participate in the production of O2- by solar radiation and imply that O2- may play a role in sunlight-induced erythema and dermal carcinogenesis.

Anions↗
PubMed1984

Inhibition of the genotoxicity of bleomycin by superoxide dismutase.

Bleomycin was found to be cytotoxic and mutagenic in the CHO/HGPRT forward mutation assay. Approximately 50% cell mortality was achieved after a 1-h exposure to 10 micrograms/ml BLM. Bleomycin was also found to induce mutation to thioguanine resistance in a dose-dependent manner. Both the cyto- and geno-toxicity resulting from BLM exposure could be reduced by the prior addition of superoxide dismutase, implicating a role for activated oxygen metabolites in the mechanism of toxicity of bleomycin.

Animals↗
PubMed1983

Superoxide anion generated by potassium superoxide is cytotoxic and mutagenic to chinese hamster ovary cells.

Chinese hamster ovary cells in vitro were exposed to superoxide anion (O2-) generated by the addition of potassium superoxide (KO2) to the cell culture media. It was determined that 2 nmoles O2- per ml media resulted in approximately 50% cell mortality. The number of 6-thioguanine-resistant mutants was also increased in a dose-related fashion. Both these effects of KO2 were inhibitable by the prior addition of superoxide dismutase, indicating that superoxide anion is cytotoxic and genotoxic in mammalian cells.

Animals↗
PubMed1983

Bleomycin cytotoxicity is prevented by superoxide dismutase in vitro.

The cytotoxicity of the antitumor antibiotic bleomycin (BLM) on Chinese hamster ovary cells in vitro was studied. Approximately 50% of the cells were killed by exposure to 9.6 micrograms/ml BLM for 1 h. The cytotoxicity could be partially reversed by the prior addition of superoxide dismutase (SOD) or catalase, but not with the addition of mannitol or histidine. These results indicate that superoxide anion and hydrogen peroxide but not hydroxyl radical are involved in the cytotoxic action of BLM.

Animals↗
PubMed1983

Benzo(a)pyrene and aniline increase sister chromatid exchanges in cultured rat liver fibroblasts without addition of activating enzymes.

The RL4 rat liver epithelial cell line possesses enzymes capable of bioactivating xenobiotics. This cell line was used without the addition of exogenous activating enzymes to study the genotoxicity of benzo(a)pyrene B(a)P and aniline as measured by the sister chromatid exchange technique. Both increased sister-chromatid exchange (SCE) formation in RL4 cells although B(a)P was more effective than aniline. Pyrene, a structural analogue of B(a)P, demonstrated no genotoxicity. These results indicate that the RL4 cell line containing endogenous bioactivation ability may be useful for genotoxicity studies.

Aniline Compounds↗
PubMedDate not supplied

Activation of methanol by hepatic postmitochondrial supernatant: formation of a condensation product with 2,4-diaminotoluene.

2,4-Diaminotoluene, an aromatic amine hepatocarcinogen in rats and mice, reacts extensively with formaldehyde produced by the oxidation of methanol to form a single reaction product. Using 1H and 13C NMR and high-resolution mass spectroscopy, this product was shown to be bis(2,4-diamino-5-tolyl)methane. This reaction product is shown to occur under conditions whereby methanol is metabolized to formaldehyde by rat hepatic postmitochondrial supernatant. These results demonstrate a novel reaction of aromatic amines and formaldehyde in biological samples and indicate that methanol as a solvent may become activated in vitro and produce complex interactions with solutes.

Animals↗
PubMedDate not supplied

Metabolism, disposition, and mutagenicity of 2,6-diaminotoluene, a mutagenic noncarcinogen.

2,6-Diaminotoluene (2,6-DAT) is a major industrial chemical; approximately 100 million pounds are used annually in the synthesis of 2,6-toluene diisocyanate. 2,6-DAT is mutagenic in Salmonella typhimurium TA98 requiring metabolic activation, but has been previously shown to be a noncarcinogen in male and female F344 rats and male and female 86C3F1 mice dosed orally in 2-year bioassays. 2,6-DAT was rapidly and extensively absorbed following oral administration, indicating that its lack of carcinogenicity is not due to poor absorption from the gastrointestinal tract. 2,6-DAT was also rapidly excreted, with 85% of 2,6-DAT-associated radioactivity being recovered in the urine within 24 hr. Resolution of the urine by reverse phase HPLC demonstrated the presence of four metabolites, but none of the parent 2,6-DAT. Therefore, the lack of carcinogenicity of 2,6-DAT is not due to lack of biotransformation in vivo. Following separation by HPLC, the metabolites were analyzed by electron impact and fast atom bombardment mass spectroscopy and by NMR spectroscopy. The metabolites were identified as a) 3-hydroxy-2,6-DAT, b) 4-hydroxy-2-acetylamino-6-aminotoluene, c) 2-acetylamino-6-aminotoluene, and d) 2,6-di(acetylamino)-toluene. Metabolites b and d were found to be mutagenic in Salmonella typhimurium TA98 and then only in the presence of an activation system. Results of this study indicate that 2,6-DAT, which is a mutagen in in vitro tests, is also metabolized by the rat to compounds which are proximate mutagens.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Retinoic acid exposure of the mouse on embryonic day 9 selectively spares derivatives of the frontonasal neural crest.

Retinoic acid is known to perturb craniofacial development and can be used to understand processes controlling early embryonic development of the face. The effects of retinoic acid on mouse craniofacial development were studied by administration of a single dose (25-200 mg/ kg) of all-trans retinoic acid (RA) to timed pregnant C57BL6/J mice at gestational days (gd) 8.25, 9, or 10. RA exposure on gd 8.25 or gd 10 resulted in craniofacial defects in fetuses but gd 9 exposure revealed a differential effect of RA depending upon whether tissues were derived from branchial arch or frontonasal neural crest. Embryos exposed to RA at gd 9 showed a dose-dependent effect of RA on branchial arch derived tissues; first arch derivatives were most severely affected with the mandible and zygoma becoming severely dysplastic at the highest dose of RA (200 mg/kg). However, RA exposure on gd 9 completely spared frontonasal neural crest-derived tissues. Paired premaxillae nasal and frontal bones as well as the cartilaginous nasoethmoid region and nasal capsule containing the osseous vomer showed no statistical difference from those of control animals. These studies showed a temporal and differential sensitivity to RA and may suggest a developmental heterogeneity of the cephalic neural crest cells destined to participate in formation of craniofacial structures.

Animals↗