Beam steering by liquid crystal elastomer fibres.

The problem of utilizing a laser beam as an information vehicle and dividing it into different channels is an open problem in the telecommunication field. The switching of a signal into different ports has been demonstrated, to date, by employing complex devices and mechanisms such as the electro optic effect, microelectromechanical system (MEMS) mirrors, or liquid crystal-based spatial light modulators (SLMs). We present here a simple device, namely a mirror held by a liquid crystal elastomer (LCE) fibre, as an optically and remotely driven beam steerer. In fact, a considered signal (laser beam) can be addressed in every in-plane direction by controlling the fibre and mirror rotation, i.e., the deflected probe beam angle. Such movement is possible due to the preparation of LCE fibres able to rotate and contract under a selective light stimulus. By adjusting the irradiation stimulus power, elastic fibres are able to rotate with a specific angle, performing more than one complete revolution around their axis. The described movement is perfectly reversible as soon as the stimulus is removed.

A NTCP approach for estimating the outcome in radioiodine treatment of hyperthyroidism.

Radioiodine has been in use for over 60 years as a treatment for hyperthyroidism. Major changes in clinical practice have led to accurate dosimetry capable of avoiding the risks of adverse effects and the optimization of the treatment. The aim of this study was to test the capability of a radiobiological model, based on normal tissue complication probability (NTCP), to predict the outcome after oral therapeutic 131I administration. Following dosimetric study, 79 patients underwent treatment for hyperthyroidism using radioiodine and then 67 had at least a one-year follow up. The delivered dose was calculated using the MIRD formula, taking into account the measured maximum uptake of administered iodine transferred to the thyroid, U0, and the effective clearance rate, Teff and target mass. The dose was converted to normalized total dose delivered at 2 Gy per fraction (NTD2). Furthermore, the method to take into account the reduction of the mass of the gland during radioiodine therapy was also applied. The clinical outcome and dosimetric parameters were analyzed in order to study the dose-response relationship for hypothyroidism. The TD50 and m parameters of the NTCP model approach were then estimated using the likelihood method. The TD50, expressed as NTD2, resulted in 60 Gy (95% C.I.: 45-75 Gy) and 96 Gy (95% C.I.: 86-109 Gy) for patients affected by Graves or autonomous/multinodular disease, respectively. This supports the clinical evidence that Graves' disease should be characterized by more radiosensitive cells compared to autonomous nodules. The m parameter for all patients was 0.27 (95% C.I.: 0.22-0.36). These parameters were compared with those reported in the literature for hypothyroidism induced after external beam radiotherapy. The NTCP model correctly predicted the clinical outcome after the therapeutic administration of radioiodine in our series.

Experimental determination of calibration settings of a commercially available radionuclide calibrator for various clinical measurement geometries and radionuclides.

Following the approach of the National Primary Laboratory of the UK (NPL) for the calibration of radionuclide calibrators, but using a commercially available instrument with no data available in the literature, the radionuclide calibrator response was investigated as a function of different measurement geometries at the "Regina Elena" National Cancer Institute (IRE) in Rome. Working with Italian National Metrology Institute for ionising radiation quantities (ENEA-INMRI), specific calibration factors with traceability to national primary standards were determined for different types of glass vials, solid capsules and plastic syringes, investigating three radionuclides with different energy spectra (Tc-99m, In-111, I-131). For each kind of syringe, calibration correction factors for different filling volumes were calculated. For Tc-99m and I-131 the difference between measured and true activity was in the range 2-7%, depending on measurement geometry. For In-111 a large percentage deviation from the true activity value was found in each geometry considered, reaching 35%. The magnitude of this difference is particularly dependent on the energies of the emitted photons.

Psoralen interstrand cross-link repair is specifically altered by an adjacent triple-stranded structure.

Targeting DNA-damaging agents to specific DNA sites by using sequence-specific DNA ligands has been successful in directing genomic modifications. The understanding of repair processing of such targeted damage and the influence of the adjacent complex is largely unknown. In this way, directed interstrand cross-links (ICLs) have already been generated by psoralen targeting. The mechanisms responsible for ICL removal are far from being understood in mammalian cells, with the proposed involvement of both mutagenic and recombinogenic pathways. Here, a unique ICL was introduced at a selected site by photoactivation of a psoralen moiety with the use of psoralen conjugates of triplex-forming oligonucleotides. The processing of psoralen ICL was evaluated in vitro and in cells for two types of cross-linked substrates, either containing a psoralen ICL alone or with an adjacent triple-stranded structure. We show that the presence of a neighbouring triplex structure interferes with different stages of psoralen ICL processing: (i) the ICL-induced DNA repair synthesis in HeLa cell extracts is inhibited by the triplex structure, as measured by the efficiency of 'true' and futile repair synthesis, stopping at the ICL site; (ii) in HeLa cells, the ICL removal via a nucleotide excision repair (NER) pathway is delayed in the presence of a neighbouring triplex; and (iii) the binding to ICL of recombinant xeroderma pigmentosum A protein, which is involved in pre-incision recruitment of NER factors is impaired by the presence of the third DNA strand. These data characterize triplex-induced modulation of ICL repair pathways at specific steps, which might have implications for the controlled induction of targeted genomic modifications and for the associated cellular responses.

Molecular analysis by electron microscopy of the removal of psoralen-photoinduced DNA cross-links in normal and Fanconi's anemia fibroblasts.

The induction and fate of psoralen-photoinduced DNA interstrand cross-links in the genome of Fanconi's anemia (FA) fibroblasts of complementation groups A and B, and of normal human fibroblasts, were investigated by quantitative analysis of totally denatured DNA fragments visualized by electron microscopy. 8-Methoxypsoralen (5 x 10(-5) M) interstrand cross-links were induced as a function of the near ultraviolet light dose. With time of postexposure incubation, a fraction of interstrand cross-links disappeared in all cell lines. However, 24 h after treatment, this removal was significantly lower in the two FA group A cell lines examined (34-39%) than in the FA group B and normal cell lines (43-53 and 47-57%, respectively). These data indicate that FA cells are at least able to recognize and incise interstrand cross-links, as normal cells do, although group A cells seem somewhat hampered in this process. This is in accord with data obtained on the same cell lines using another biochemical assay (D. Papadopoulo, D. Averbeck, and E. Moustacchi. Mutat. Res., DNA Repair Rep., 184: 271-280, 1987). Since the fate of cross-links in FA constituted a controversial matter, it is important to stress that two different methodologies applied to genetically well defined cell lines led to the same conclusions.

Impairment of RNA synthesis and its recovery in angelicin photosensitized mammalian cells. A probe for DNA damage and repair.

The template activity of DNA for ribosomal RNA transcription has been investigated in monkey kidney CV-1 cells after angelicin photosensitization in order to monitor the induction of lesions in the DNA and their possible subsequent disappearance, i.e. repair. Separate confluent cultures were submitted to a single angelicin treatment at different time intervals before incubation with [3H]uridine. The labeled RNA prepared from whole cells was analysed by polyacrylamide-agarose gel electrophoresis. The results indicate that: Angelicin monoadditions on DNA constitute transcription-terminating lesions which depress overall RNA synthesis, give rise to shortened RNA chains and modify the expression of transcriptional linked genes. CV-1 cells are able to repair, at least partially, the induced transcription-terminating lesions and progressively recover RNA synthesis with a reversion of the initially observed modifications. The repair seems to be independent of semiconservative DNA synthesis since fluorodeoxyuridine does not affect the recovery of RNA transcription. The present work also confirms the arrangement of rRNA genes in tandem behind a common operator in the order 18--28 S as previously determined in the same cells by a radiological mapping technique and reinforces the potential applicability of transcription analysis to the study of repair processes operating on physically or chemically induced damage in DNA.

Inhibition and recovery of ribosomal RNA synthesis in ultraviolet-irradiation mammalian cells.

The effects of ultravilet light on rRNA synthesis were studied in stationary, monkey kidney CV-1 cells. Separate cultures were irradiated with a single ultraviolet dose of up to 525 erg/mm2 at different time intervals before incubation with [3H]uridine. The labeled RNA prepared from whole cells was analyzed by polyacrylamide-agarose gel electrophoresis. In cells ultraviolet irradiated 30 min before transcription analysis, the rate of total RNA and of 45 S RNA synthesis are depressed whereas a synthesis of unusual RNAs, shorter than 45 S RNA, appears. The rates of 28 S and of 18 S RNA synthesis decrease as a function of ultravilet dose and at the same time the ratio of 18 S to 28 S RNA increases. These results are consistent with the idea of a premature RNA chain termination on ultraviolet-damaged DNA. The ultraviolet-induced alterations of transcription disappear progressively with time after irradiation: the rates of total RNA and of 45 S RNA synthesis increase whereas the synthesis of unusual RNAs decreases; in parallel the rates of 28 S and 18 S RNA synthesis recover with a shift of the 18 S to 28 S RNA ratio toward the normal value 1 : 1, probably as a direct consequence of the repair of ultraviolet-induced lesions in the DNA. The kinetics of recovery are dose dependent and are comparable to those of the excision-repair of DNA photoproducts as measured by unscheduled DNA synthesis in ultraviolet-irradiated CV-1 cells. Fluorodeoxyuridine does not affect recovery. The data also show that in CV-1 cells, rRNA genes are arranged after their promotor in the order 18 S rRNA -- 28 S rRNA.

Low catalase activity in xeroderma pigmentosum fibroblasts and SV40-transformed human cell lines is directly related to decreased intracellular levels of the cofactor, NADPH.

We have previously shown that fibroblasts from ultra-violet (UV) hypersensitive xeroderma pigmentosum patients (XP) are markedly deficient in catalase activity resulting in high intracellular levels of hydrogen peroxide (H2O2) following UV irradiation. No direct correlation between catalase activity and repair ability was found since XP variant cells which are proficient in nucleotide excision repair (NER) showed activities as low as those found in NER deficient classical XP groups A and D. However, in contrast to the skin cancer prone XP patients, another NER deficient syndrome, trichothiodystrophy (TTD), which does not exhibit any cancer predisposition, was found to present normal catalase activity. Moreover, it was found that a variety of SV40 transformed human cell lines also showed decreased catalase activities. Our previous data showed that a molecular analysis of the normal, XP, TTD or transformed human fibroblast cell lines did not reveal any differences in levels of catalase transcription or amount of catalase protein subunits. These results incited us to examine the structure/function relationship of the tetrameric active enzyme form of catalase (which is the only one able to carry out H2O2 dismutation) with its cofactor NADPH. In the present study, we have measured the effects on catalase activity after adding NADPH either to acellular extracts or during cell culture of the different cell types. The NADPH levels were also quantified directly in intact cells using flow cytometry. Our results show a clear relationship between low catalase activity and striking decrease in intracellular NADPH levels.

DNA ligase activity in carcinogen-treated human fibroblasts.

In an enzymological approach to study DNA repair mechanisms induced by carcinogen-treatment of mammalian cells, we have investigated how DNA ligase activity is affected by the treatment with several compounds producing different DNA lesions. Stationary cultures of human fibroblasts were exposed to various doses of carcinogens (UV-light at 254 nm, N-acetoxy-acetyl-aminofluorene, ethyl-methane sulfonate, N-methylnitro-nitrosoguanidine, mitomycin C and 4-nitroquinoline-N-oxide) at different time-intervals before preparing crude cellular extracts and assaying for ligase activity. Results have shown that: 1. UV-irradiation, AAAF, 4NQO or MMC treatment of cells induces a two-fold increase in the ligase activity compared to control cells within 48 hours following the treatment. 2. A partial purification of the enzyme from these cellular crude extracts by sedimentation through sucrose gradients has shown: a. DNA ligase activity from control cells presents a profile composed of two distinct peaks sedimenting respectively at about 4S and 7S; b. the carcinogen treatment of either repair-proficient human fibroblasts or repair-deficient xeroderma pigmentosum cells (complementation group A) seems to induce a specific increase of the 4S-form of DNA ligase.

Photochemotherapy using pyridopsoralens.

Aiming to decrease the acute side effects and genotoxic hazards of PUVA, pyrido (3,4-C) psoralen (PP) and 7-methyl pyrido (3,4-C) psoralen (MPP) were synthesized and studied. Their UVA maximum absorption lies at 325 and 330 nm, respectively. Their photostability is comparable to that of 8-MOP. They complex to DNA in the dark, and, in the presence of UVA, produce only monoadditions to DNA, as shown by fluorescence and DNA denaturation-renaturation studies. In diploid eukaryotic yeast they are more effective than 8-MOP for the induction of lethal effects and mitochondrial damage. Their mutagenic activity per unit dose of UVA is in the same range as that of 8-MOP. However, per viable cell they are clearly less mutagenic than 8-MOP. This difference is also observed for recombinogenic activity. No oxygen effect is observed. In mammalian cells the following ranges of effectiveness are found: inhibition of DNA synthesis in human fibroblasts: MPP greater than PP greater than 8-MOP; mutagenic activity in V79 Chinese hamster cells: MPP greater than PP greater than 8-MOP; cell transforming ability in C3H embryonic mouse cells: MPP greater than 8-MOP greater than PP as a function of UVA dose, and: 8-MOP greater than MPP greater than PP as a function of survival; induction of sister chromatic exchanges (SCE) per unit dose: MPP greater than PP greater than 8-MOP in the linear part of the induction curve, and : 8-MOP greater than PP greater than MPP at the maximum level of SCE obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of the lipophilic biscation, bis-pyridinium oxime BP12, on bioenergetics and induction of permeability transition in isolated mitochondria.

In order to further investigate the mechanism of action of bridged lipophilic bis-pyridinium oximes previously observed to interfere with mitochondrial metabolism and to induce growth arrest and apoptosis in HeLa cells (Nocentini et al., Biochem Pharmacol 53: 1543-1552, 1997), we studied the effects of a bis-pyridinium oxime with a polymethylene chain N = 12 (BP12) on isolated rat liver mitochondria. Respiration in the absence of ADP with succinate plus rotenone as substrate was not affected after treatment with various concentrations of BP12 up to 10 microM, while the ADP-stimulated respiration was slowed down, with a parallel decrease in ATP synthesis. No effects of BP12 were detected on membrane potential, ATPase activity, and inorganic phosphate transport, but the adenine nucleotide translocase was inactivated and a permeability transition of the inner membrane was induced in the presence of calcium. These data suggest that mitochondrial impairment of ATP synthesis and the formation of the permeability transition pore may be responsible for apoptotic cell death already observed in cells treated with BP12.

Induction of mitochondrial dysfunction and apoptosis in HeLa cells by bis-pyridinium oximes, a newly synthesized family of lipophilic biscations.

When tested on HeLa cells, bis-pyridinium oximes (BPO), a family of newly synthesized molecules whose charged pyridinium moieties are linked by a linear polymethylene chain of variable length (N = 3 to 12) have been shown to possess an inhibitory effect on cell growth and finally to provoke cell death. BPO-affected cells displayed reduced mitochondrial oxygen consumption and ATP stores and were blocked in the G1 phase of the cell cycle. Mitochondrial membrane potential, as assayed with the dye 3,3'-diexyloxacarbocyanine iodide [DiOC6(3)], increased in BPO-treated cells with time of exposure. Cell growth inhibition as well mitochondrial dysfunction were observed only with derivatives having a long polymethylene linking chain (N > or = 6). Furthermore, the concentration of the compound eliciting such effects was inversely related to the number of methylene groups in the linking chain. None of the BPO with N = 6 to 12 modified the mitochondrial DNA content, relative to the nuclear DNA content. In BPO (N = 8 and N = 12)-treated cells, chromatin fragmentation and internucleosomal DNA cleavage occurred massively, indicating that the death mode induced by these compounds is apoptosis. The possible pathway of action and the potential pharmacological interest of these compounds are discussed.

Rejoining kinetics of DNA single- and double-strand breaks in normal and DNA ligase-deficient cells after exposure to ultraviolet C and gamma radiation: an evaluation of ligating activities involved in different DNA repair processes.

The repair kinetics for rejoining of DNA single- and double-strand breaks after exposure to UVC or gamma radiation was measured in cells with deficiencies in DNA ligase activities and in their normal counterparts. Human 46BR cells were deficient in DNA ligase I. Hamster EM9 and EM-C11 cells were deficient in DNA ligase III activity as a consequence of mutations in the XRCC1 gene. Hamster XR-1 cells had mutation in the XRCC4 gene, whose product stimulates DNA ligase IV activity. DNA single- and double-strand breaks were assessed by the comet assay in alkaline conditions and by the technique of graded-field gel electrophoresis in neutral conditions, respectively. 46BR cells, which are known to re-ligate at a reduced rate the DNA single-strand breaks incurred during processing of damage induced by UVC but not gamma radiation, were shown to have a normal repair of radiation-induced DNA double-strand breaks. EM9 cells exhibited a reduced rate of rejoining of DNA single-strand breaks after exposure to ionizing radiation, as reported previously, as well as UVC radiation. EM-C11 cells were deficient in the repair of radiation-induced-DNA single-strand breaks but, in contrast to EM9 cells, demonstrated the same kinetics as the parental cell line in the resealing of DNA breaks resulting from exposure to UVC radiation. Both EM9 and EM-C11 cells displayed a significant defect in rejoining of radiation-induced-DNA double-strand breaks. XR-1 cells were confirmed to be highly deficient in the repair of radiation-induced DNA double-strand breaks but appeared to rejoin DNA single-strand breaks after UVC and gamma irradiation at rates close to normal. Taken together these results indicate that: (1) DNA ligase I is involved only in nucleotide excision repair; (2) DNA ligase IV plays an important role only in repair of DNA double-strand breaks; and (3) DNA ligase III is implicated in base excision repair and in repair of DNA double-strand breaks, but probably not in nucleotide excision repair.

Comet assay analysis of repair of DNA strand breaks in normal and deficient human cells exposed to radiations and chemicals. Evidence for a repair pathway specificity of DNA ligation.

The induction and resealing of DNA strand breaks in a cell line with a proven defect in DNA ligase I, 46BR, and in two Bloom's syndrome cell lines, YBL6 and GM 1492, were compared to those observed in normal human 1BR/3 fibroblasts after treatment with a variety of genotoxic agents whose lesions are processed by different repair pathways. This analysis was performed using the single-cell gel electrophoresis assay. The three types of cells were found to have similar capabilities to recognize and incise ultraviolet photoproducts and also demonstrated similar amounts of DNA breaks immediately after gamma irradiation. During post-treatment incubation, 46BR cells showed a marked DNA re-ligation defect after ultraviolet radiation damage, GM 1492 cells demonstrated a highly reduced DNA joining ability after relatively high doses of ultraviolet radiation, and YBL6 cells were particularly affected in DNA re-ligation after damage by 4-nitroquinoline-1-oxide. The two Bloom's syndrome cell lines and 46BR cells had a nearly normal ability to reseal breaks resulting from gamma irradiation or treatment with xanthine plus xanthine oxidase. These findings suggest that different DNA ligases may be involved in different DNA repair pathways in human cells.

Exacerbating effect of vitamin E supplementation on DNA damage induced in cultured human normal fibroblasts by UVA radiation.

The effects of vitamin E supplementation were evaluated in cultured human normal fibroblasts exposed to ultraviolet A radiation (320-380 nm) (UVA). Cells were incubated in medium containing alpha-tocopherol, alpha-tocopherol acetate or the synthetic analog Trolox for 24 h prior to UVA exposure. DNA damage in the form of frank breaks and alkali-labile sites, collectively termed single-strand breaks (SSB), was assayed by the technique of single cell gel electrophoresis (comet assay), immediately following irradiation or after different repair periods. The generation of hydrogen peroxide (H2O2) and superoxide ion (O2.-) was measured by flow cytometry through the oxidation of indicators into fluorescent dyes. It was observed that pretreatment of cells with any form of vitamin E resulted in an increased susceptibility to the photoinduction of DNA SSB and in a longer persistence of damage, whereas no significant change was observed in the production of H2O2 and O2.- reactive oxygen species, compared to untreated controls. These findings indicate that in human normal fibroblasts, exogenously added vitamin E exerts a promoting activity on DNA damage upon UVA irradiation and might lead to increased cytotoxic and mutagenic risks.

DNA photobinding of 7-methylpyrido[3,4-c]psoralen and 8-methoxypsoralen. Effects on macromolecular synthesis, repair and survival in cultured human cells.

The photobinding to DNA of tritiated 7-methylpyrido[3,4-c]psoralen (MPP), a recently synthesized monofunctional compound of therapeutical interest, and of 8-methoxypsoralen (8-MOP) was determined in cultured normal human fibroblasts. Employing compounds at 10(-6) M, MPP photobinds approximately 11 times more efficiently than 8-MOP: one molecule is fixed respectively per 7.5 X 10(4) or 8.1 X 10(5) base pairs/kJ . m-2 of 365-nm radiation (UVA). Removal of bound material from DNA is slow and limited in 48-72 h of post-treatment incubation to 30-40% of initial adducts formed by MPP and to 50-60% of those of 8-MOP. For equivalent photobinding MPP and 8-MOP induce similar inhibitions of DNA synthesis. However, the recovery of DNA synthesis during post-treatment incubation is lower after photoaddition of MPP than after that of 8-MOP. MPP also exerts a much higher lethal effect than 8-MOP: one lethal hit corresponds to about 4400 and to 19,900 adducts per cell respectively. Alkaline elution experiments confirmed the monofunctional nature of MPP and indicated that in MPP-damaged cells DNA breaks accumulate with time of post-treatment incubation. In contrast, after photoaddition of 3-carbethoxypsoralen (3-CPs), another monofunctional furocoumarin, or irradiation with 254-nm UV, DNA breaks are induced only transiently. In 8-MOP-treated cells, DNA cross-links appear to be partially repaired. In conclusion, MPP monoadducts turn out to constitute more cytotoxic lesions than 8-MOP mono- and bi-adducts.

Cellular responses to hematoporphyrin-induced photooxidative damage in Fanconi anemia, xeroderma pigmentosum and normal human fibroblasts.

Several observations reported in the literature suggest that singlet oxygen (1O2) might play a role in the clastogenic process in Fanconi anemia (FA) cells, and that the antioxidant status of xeroderma pigmentosum (XP) may also be altered. In order to test the ability of FA and XP cells, relative to normal cells, to cope with 1O2 damage, the effects of photosensitization by hematoporphyrin (HP) have been determined (i) on host cell reactivation (HCR) of damaged infecting herpes simplex virus (HSV) or transfecting SV40 DNA, and (ii) on DNA template capability and clonogenicity of treated cells. Results showed no significant difference among the three types of cells, either for the survival of HP-photosensitized HSV, or for the yields of SV40 virus following transfection of cultures with damaged viral DNA. The treatment of cells with HP plus 365-nm light leads to a dose-dependent, homothetic reduction of 18S and 28S ribosomal RNA (rRNA) synthesis, presumably through a mechanism other than the formation of transcription termination sites. After a 24-h post-exposure incubation, the rate of rRNA synthesis was restored to higher than normal levels in all cell lines. Finally, two FA cell lines showed a higher survival to HP photosensitization than two normal cell lines. Another FA cell line and XP-A and XP-C cells were in the range of sensitivity of the two normal strains for this treatment. These results indicate that FA cells possess an antioxidant defense system at least as efficient as that of normal cells for processing 1O2-induced damage.

Is the induction of pyrimidine cyclobutane dimers relevant for the high cytotoxic effect of 7-methylpyrido[3,4-c]psoralen plus UV-A?

Recently, it was shown that the photoactivation of 7-methylpyrido[3,4-c]psoralen (MPP), a highly phototoxic monofunctional compound, as well as leading to the direct cycloaddition of the molecule to pyrimidine bases, also induces the dimerization of adjacent pyrimidines in DNA in vitro (Moysan et al., 1988). For other psoralens, e.g., 8-methoxypsoralen (8-MOP), such a formation of pyrimidine dimers does not occur (Costalat et al., 1989). The relatively low number of pyrimidine dimers which one can estimate from such in vitro results to be formed in vivo in cell DNA after highly lethal MPP photosensitization does not indicate that these dimers have important direct biological consequences. They could, however, interact with MPP adducts and eventually greatly potentiate their action. In order to test this hypothesis, experiments were designed to mimic the photosensitization by MPP. CV-1 TC-7 cells were irradiated at 254 nm, to produce pyrimidine dimers, and subsequently treated with 8-MOP or angelicin plus 365-nm light, to produce psoralen adducts. The clonogenicity of these cells was compared to that of cells damaged only by irradiation at 254 nm or by psoralens plus 365-nm light. It was observed that, for the same amount of induced adducts, the lethal effect of photosensitization by MPP remains much higher than that of photosensitization by 8-MOP coupled to a large excess of pyrimidine dimers induced with 254-nm light. In fact, with both 8-MOP and angelicin, close to additive effects were observed between pyrimidine dimers and psoralen adducts.(ABSTRACT TRUNCATED AT 250 WORDS)

Survival and herpes virus production of normal and xeroderma pigmentosum fibroblasts after treatment with formaldehyde.

The survival of excision-deficient and of excision-proficient (variant) skin fibroblasts from xeroderma pigmentosum (XP) donors was about 5 times and twice, respectively, more sensitive to formaldehyde (FA) treatment than that of skin fibroblasts from healthy and XP heterozygote donors. The capacity of FA-treated host cells to further support Herpes virus (HSV) replication was also more sensitive to FA in XP12BE (group A) than in normal (KD) cells. An important recovery of this capacity occurred in both cell types when they were infected at increasing times (up to 36 h) after FA treatment. This contrasts with the decreasing capacity observed in XP12BE when similarly infected at increasing times after exposure to ultraviolet. In addition, the survival of FA-treated HSV was comparable in KD and XP12BE cells, whereas that of UV-irradiated HSV was much lower in XP12BE than in KD cells.

Induction of cytogenetic effects in human fibroblast cultures after exposure to formaldehyde or X-rays.

Cytogenetic changes induced by formaldehyde (FA) in exponentially growing human fibroblasts were compared with those produced by X-rays. Chromosome aberrations of different types were detected. Exposure to 2 mM FA for 15 min resulted, quantitatively and qualitatively, in effects comparable to those produced by an X-ray dose of 100 rad. X-Rays at higher exposures produced types of chromosome aberrations that differed from those induced by higher exposures to FA.