Inhibitory effects of naturally occurring coumarins on the metabolic activation of benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in cultured mouse keratinocytes.

Several naturally occurring coumarins to which humans are routinely exposed have been previously found to be potent inhibitors and inactivators of cytochrome P450 (P450) 1A1-mediated monooxygenase in both murine hepatic microsomes and in a reconstituted system using purified human P450 1A1 [Cai et al. (1993) Chem. Res.

Mechanism-based inactivation of hepatic ethoxyresorufin O-dealkylation activity by naturally occurring coumarins.

Several naturally occurring coumarins contained in the human diet have been found to be effective inhibitors and inactivators of murine hepatic ethoxyresorufin O-dealkylase (EROD) and pentoxyresorufin O-dealkylase in vitro [Cai, Y., Bennett, D., Nair, R.

DNA repair by oocytes.

Experimental evidence in a number of different in vivo and in vitro systems indicates clearly that the vertebrate oocyte is capable of repairing endogenous and exogenous DNA damaged as a result of meiotic recombination, the action of UV and X-irradiation or the effects of mutagenic chemicals. It would appear that both before and after the dictyate stage of meiosis the oocyte has less repair capacity and/or is more sensitive to DNA damaging agents. Epigenetic factors associated with the expression of genetic faults arising in oocytes have been largely ignored in the past.

Environmental survey of RCMP detachment building in Powell River, B.C., implicated in a cancer cluster.

The rationale and approach are presented that were used to investigate the Powell River RCMP detachment building, perceived to have a higher than normal cancer incidence and whose occupants demanded to know whether the building was safe to work in. On the basis of the history of the building and the cancers observed, a set of carcinogens were looked for in areas where the worst conditions were expected. A positive result would initiate a second more in-depth survey.

Inhibition and inactivation of murine hepatic ethoxy- and pentoxyresorufin O-dealkylase by naturally occurring coumarins.

The present study was designed to evaluate the effects of a series of natural coumarins on ethoxyresorufin O-dealkylase (EROD) and pentoxyresorufin O-dealkylase (PROD) activities in vitro using hepatic tissues from SENCAR mice. Fifteen different coumarins were examined for potential modulating activities. Several naturally occurring coumarins, found in the human diet, were effective inhibitors of hepatic EROD activity in vitro, including coriandrin, bergamottin, isoimperatorin, and ostruthin.

UV-A-mediated activity of p-methoxymethylcinnamate.

Methyl esters of hydroxycinnamic acids are photobiologically active. Cis(Z) and trans(E) p-methoxymethyl-cinnamate photosensitize Escherichia coli and Chinese hamster ovary cells. They also produce sister chromatid exchanges.

The unusual UVA-dependent antiviral properties of the furoisocoumarin, coriandrin.

The novel furoisocoumarin, coriandrin, which was found recently to possess an interesting combination of photobiological properties, was investigated for antiviral activity in the presence and absence of UVA (long-wavelength ultraviolet radiation). In contrast to results obtained with other antiviral furocoumarins, such as 8-MOP (8-methoxypsoralen), coriandrin was much more phototoxic to the RNA-virus Sindbis virus than to the DNA-virus murine cytomegalovirus, although both viruses were substantially more sensitive to this compound than they were to 8-MOP. Human immunodeficiency virus, HIV-1, was also susceptible to coriandrin + UVA.

The photobiological activity of 5-geranoxypsoralen and its photoproducts.

5-geranoxypsoralen (Bergamottin) does not photosensitize bacteria or a bacterial virus. It does, however, photosensitize mammalian cells in tissue culture. Irradiation with either black light (300-400 nm) or fluorescent ceiling lights produced at least four photobiologically active degradation products, the chemical nature of which still remains to be elucidated.

Photobiological properties of a novel, naturally occurring furoisocoumarin, coriandrin.

The photobiological properties of a novel, naturally occurring furoisocoumarin isolated from coriander and named coriandrin are described. Photosensitized lethal and mutagenic effects in bacteria indicate that it is more active than psoralen. It is a weak frameshift mutagen in the dark.

The use of Albuminar 5 as a medium supplement in clinical IVF.

Human serum and Albuminar 5 (A5) were compared as medium supplements to Earle's solution containing pyruvate in clinical IVF. One-hundred patients in each group showed a fertilization rate of 60% with serum and of 62% with A5. The overall pregnancy rates in the serum and A5 groups were 20 and 24%, respectively.

Physical factors are involved in the destruction of embryos and oocytes during freezing and thawing procedures.

Observations made during the freezing and thawing of mouse and human oocytes and mouse embryos with the cryomicroscope suggest that physical factors as well as physicochemical factors may play a role in the development of lethal damage upon thawing. The point of contact with the approaching ice front may predispose that area to the appearance of future cytoplasmic blebbing. The ice front distorts the oocyte and this distortion remains during its subsequent thermal history and is unrelated to desiccation distortion.

Concerted contractions of tumour fragments derived from a pure mucoid carcinoma of the breast in vitro.

Organized tissue fragments obtained by dissociation of a pure mucoid carcinoma of the breast were cultured in vitro. The cellular organization of the fragments appears similar to that observed in vivo, and consist of mucous-filled spherules surrounded by a single layer of tumour cells. Time-lapse video recordings revealed that the cells surrounding these fragments undergo a concerted contraction and relaxation over the time span of several hours.

Oxypeucedanin, a Major Furocoumarin in Parsley, Petroselinum crispum.

Fresh parsley leaves and roots were analyzed by HPLC and photobiological assay for photoactive furocoumarins. Oxypeucedanin ( 7), not previously reported from parsley, was found to be the major component (70-100 ppm wet weight). Although only moderately photoactive, its high concentration in parsley may be partially responsible for contact photodermatitis.

Detection of furocoumarins in plants and plant products with an ultrasensitive biological photoassay employing a DNA-repair-deficient bacterium.

The application of an ultrasensitive photobiological assay which detects photosensitizing furocoumarins with sensitivities as high as 1 × 10(-11) g is discussed in relation to these molecules as phytoalexins. Examples of the utilization of this technique, verified by both HPLC and TLC, are the analyses of healthy and diseased celery and carrots, dry seeds, plant extracts and oils, and whole plants and leaves. The usefulness of this method in following the metabolic detoxification of furocoumarins is also illustrated.

Uptake of pyruvate by early human embryos determined by a non-invasive technique.

Normal levels of pyruvate in freshly collected follicular fluid were found to be 0.45 mM, a value approximately 4 X that of serum. The utilization of pyruvate by human oocytes and early embryos has been measured, non-invasively, using two similar but separate analytical methods.

Induction of DNA-DNA cross-link formation in human cells by various psoralen derivatives.

Furocoumarin-induced DNA damage, monoadducts, and cross-links were measured in normal human, xeroderma pigmentosum, and Fanconi's anemia cells after exposure to near-UV (356 nm). At similar concentrations and near-UV doses, photoaddition by 8-methoxypsoralen was twice that by angelicin and the substitution of bromodeoxyuridine for thymidine in one strand of DNA did not alter the binding. The rate of cross-linking by 8-methoxypsoralen was twice that of 5-methoxypsoralen.

Genetic damage is not produced by normal cryopreservation procedures involving either glycerol or dimethyl sulfoxide: a cautionary note, however, on possible effects of dimethyl sulfoxide.

Cryopreservation of chinese hamster ovary cells in tissue culture with either glycerol or dimethyl sulfoxide did not result in chromosome damage as measured by the sister chromatid exchange technique. These results are consistent with earlier negative reports in which the freezing and thawing of mammalian cells did not increase the frequency of micronuclei. No increases in the spontaneous mutation rates of several bacterial strains at different genetic loci were observed during the course of a number of years of storage at -196 degrees C.