[Outcome of a survey on antibiotic prescribing in veterinary medicine]. / Ergebnisse einer Umfrage zur ­Verschreibung von Antibiotika in der ­Veterinärmedizin.

INTRODUCTION: As part of the national strategy on antibiotic resistance (StAR), a therapy guide for the prudent prescription of antimicrobial agents in animals was developed. To facilitate its implementation in the veterinary practice, the therapy recommendations contained therein have been translated to the user-friendly decision support AntibioticScout.ch. In this context, we conducted a non-representative survey to assess the level of awareness as well as usage of this guide and the AntibioticScout.ch decision support. Based on case studies with typical diseases in dogs, cats and cattle, it was shown that the veterinarians participating in the survey strive to handle antibiotics responsibly and to prescribe them with restraint. Nevertheless, the survey points to possible improvements in the antibiotic therapy. In particular, the StAR guidelines or AntibioticScout.ch can be useful to the practicing veterinarians for taking into account all relevant decision criteria in the optimal selection of a suitable antimicrobial agent.

INTRODUCTION: Dans le cadre de la stratégie nationale de résistance aux antibiotiques (StAR), un guide thérapeutique pour la prescription prudente d'agents antimicrobiens chez les animaux a été élaboré. Pour faciliter son application dans la pratique vétérinaire, les recommandations thérapeutiques qu'il contient ont été transférées dans l'aide à la décision conviviale en-ligne AntibioticScout.ch. Dans ce contexte, nous avons mené une enquête non représentative pour évaluer le niveau de connaissance et l'utilisation de ce guide de l'aide à la decision AntibioticScout.ch. Sur la base d'études de cas portant sur des maladies typiques des chiens, des chats et des bovins, il a été démontré que les vétérinaires participant à l'enquête s'efforcent d' utiliser les antibiotiques de manière responsable et de les prescrire avec modération. Néanmoins, l'enquête met en évidence les améliorations possibles de la thérapie antibiotique. Le guide thérapeutique StAR ou AntibioticScout.ch peut être particulièrement utile à la profession vétérinaire pour prendre en compte tous les critères de décision pertinents dans la sélection optimale d'un agent antimicrobien approprié.

[Analyses of antimicrobial usage in 598 pig farms in Switzerland in 2017]. / Untersuchung des Antibiotikaverbrauchs in 598 Schweinebeständen in der Schweiz im Jahr 2017.

INTRODUCTION: Antimicrobial usage was analyzed in 598 Swiss pig farms as part of the SuisSano Health Program in 2017. Antimicrobial usage was calculated on the basis of the prescriptions of the veterinarians using the standard dosages DCDCH (Defined Course Dose for Switzerland) and the amount of active substance by weight. Usage was analyzed based on the active antimicrobial class, pharmaceutical form age category (suckling piglets, weaned piglets, fattening pigs, sows) and stock type (breeding farms, fattening farms, farrow-finish farms and sow pool systems (SPS). A total amount of 610 kg antimicrobials or 894,688 DCDCH standard doses were used. The proportion of Highest Priority Critically Important Antimicrobials (HPCIAs) of the total antimicrobial usage was 2.5% for breeding sows, 4.5% for piglets, and 2.7% for fattening pigs based on the number of treatments in DCDCH/animal/year. In contrast weaning piglets showed a calculated proportion of 26%, of which 18% was due to polypeptides (colistin). Suckling piglets produced in SPS stocks were treated significantly more frequently than suckling piglets from other farms (P.

INTRODUCTION: Des données sur l'utilisation d'antimicrobiens ont été collectées en 2017 dans 598 populations de porcs en Suisse dans le cadre du programme de santé SuisSano de la Société suisse de services aux exploitations porcines, SUISAG. La consommation d'antibiotiques a été calculée sur la base des prescriptions des vétérinaires en utilisant les dosages standards DCDCH (Defined Course Dose Switzerland) et la quantité de principe actif en poids. La consommation a été analysée par classe de principe actif antimicrobien, forme d'application et type d'exploitation (élevage, engraissement, combinée reproduction-engraissement et exploitations avec répartition du travail dans la production de porcelets (RTPP)). Au total, 610 kg et 894 688 doses standard d'antibiotiques DCDCH ont été utilisés sur ces exploitations. Sur la base du nombre de traitements en DCDCH/animal/an, la proportion d'antimicrobiens hautement prioritaires (HPCIA), selon la définition de l'Organisation mondiale de la santé, était basse chez les truies d'élevage, les porcelets à la mamelle et les porcs d'engraissement avec 2,5% resp. 4,5% et 2,7%. En revanche, chez les porcelets sevrés, une proportion de 26% a été calculée, dont 18% pour des polypeptides (colistine). Les porcelets de lait des exploitations de RTPP ont été traités significativement plus fréquemment que les porcelets de lait d'autres populations (P.

Antimicrobial use for selected diseases in cats in Switzerland.

BACKGROUND: Antibiotic use in human and veterinary medicine is considered a main driver of antimicrobial resistance. Although guidelines to promote appropriate use of antimicrobials in veterinary patients have been developed, antibiotic overprescription is assumed to be a common problem. The goal of this study was to investigate antimicrobial use in cats in Switzerland with acute upper respiratory tract disease (aURTD), feline lower urinary tract disease (FLUTD) and abscesses, and to assess compliance of prescription with consensus guidelines. A total of 776 cases (aURTD, n = 227; FLUTD, n = 333; abscesses, n = 216) presented to two university hospitals and 14 private veterinary practices in Switzerland during 2016 were retrospectively evaluated. Clinical history, diagnostic work-up and antimicrobial prescription (class, dosage, duration) were assessed. RESULTS: A total of 77% (aURTD), 60% (FLUTD) and 96% (abscesses) of the cases received antibiotic therapy; 13-24% received combination or serial therapy. The cats were treated for a median of 7 (abscesses) and 10 days (aURTD, FLUTD). Treatments with potentiated aminopenicillins (40-64%), third generation cephalosporins (25-28%), aminopenicillins (12-24%) and fluoroquinolones (3-13%) were most common. Prescriptions were judged in complete accordance with consensus guidelines in 22% (aURTD), 24% (FLUTD) and 17% (abscesses) of the cases. Antibiotics were prescribed although not indicated in 34% (aURTD), 14% (FLUTD) and 29% (abscesses) of the cases. The presence of lethargy, anorexia or fever in cats with aURTD, and the detection of bacteriuria in cats with FLUTD were significantly associated with antibiotic therapy. Although diagnostic work-up was significantly more common (aURTD: university hospitals, 58%; private practices, 1%; FLUTD: university hospitals, 92%; private practices, 27%) and the use of critically important antibiotics significantly less common at the university hospitals (aURTD, 10%; FLUTD, 14%) compared to private practices (aURTD, 38%; FLUTD, 54%), the frequency of antibiotic treatment was not different between the university hospitals and private practices. CONCLUSIONS: Our results indicate that overprescription of antibiotics in cats in Switzerland is common and accordance with guidelines is poor. The study highlights the need to promote antimicrobial stewardship in small animal medicine.

[Defining daily doses and total doses for the measurement of antibiotic usage in Swiss pig production]. / Etablierung von definierten Tages­dosierungen und definierten Gesamt­behandlungsdosierungen zur Messung des Antibiotikaverbrauchs in der ­Schweizer Schweineproduktion.

INTRODUCTION: A significant Antibiotic-Monitoring-System is essential to analyse the use of antibiotics and to a better understanding of trends in resistance development. In human and veterinary medicine, for example, a system based on defined daily and treatment doses (Defined Daily Dose: DDD and Defined Course Dose: DCD) is applied. These definitions can be used to estimate the number of treatment days and treatments with antimicrobial agents in a population. For veterinary medicine, the European Medicines Agency (EMA) has published the European values DDDvet and DCDvet in the farm animal sector. The aim of this study was to define Swiss daily and treatment doses (DDDch and DCDch) for the treatment of pigs and to compare them with the EMA values in order to investigate the differences between individually collected national doses and average international doses. For the comparison, the quotient of Swiss and European values was calculated and the influence of the application form of an active substance and the number of active substances contained in a preparation was investigated. One hundred and three veterinary preparations with 138 active substances were assigned a DDDch and DCDch value. A comparison with EMA values was possible for 118 active substances. The comparison showed median values of 0.91 for the daily doses and 0.90 for the treatment doses, so that the daily and treatment doses in Switzerland are lower than the corresponding EMA doses. Both the form of application (injection solutions: 1.00; premixes: 0.76; P=0.02) and the number of active substances in the preparation (one active substance: 1.00; two active substances: 0.76; three active substances: 0.43; each P.

INTRODUCTION: Pour analyser l'utilisation des antibiotiques et mieux comprendre les tendances dans le développement de résistances, un système significatif de surveillance des antibiotiques est essentiel. En médecine humaine et vétérinaire, un système basé sur des dosages journaliers et des dosages par traitement définis (Defined Daily Dose: DDD et Dose Course Dose: DCD) est par exemple utilisé. Ces définitions peuvent être utilisées pour estimer le nombre de jours de traitement et le nombre de traitements antimicrobiens dans une population. L'Agence européenne des médicaments (EMA) a publié les valeurs européennes DDDvet et DCDvet dans le secteur de l'élevage pour la médecine vétérinaire. Le but de cette étude était de définir les doses journalières et les doses par traitement en Suisse (DDDch et DCDch) pour le traitement des porcs et de les comparer aux valeurs de l'EMA pour examiner les différences entre les doses nationales collectées individuellement et les doses internationales moyennes. Pour la comparaison, le quotient des valeurs suisses et européennes a été calculé et l'influence de la forme d'application d'une substance active ainsi que le nombre de substances actives contenues dans une préparation ont été examinés. Cent trois médicaments vétérinaires contenant 138 substances actives ont reçu une valeur DDDch et DCDch. Pour 118 médicaments, une comparaison avec les valeurs EMA était possible. D'après la comparaison, les valeurs médianes pour les quotients calculés étaient de 0,91 pour les doses journalières et de 0,90 pour les doses de traitement, de sorte qu'en Suisse, les doses journalières et de traitement sont inférieures aux doses correspondantes de l'EMA. La forme d'application (solutions injectables: 1.00, prémélanges médicamenteux: 0.76, P = 0.02) et le nombre de substances actives dans la préparation (une substance active: 1.00, deux substances actives: 0.76, trois substances actives: 0.43, P.

[Vigilance for veterinary medicinal products: Reports of adverse reactions in the year 2016]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2016.

INTRODUCTION: A total of 253 reports of adverse reactions to veterinary medicinal products were received during the year 2016 representing a decrease of 13% compared to the previous year (292 reports). The majority of the reports described reactions affecting companion animals (178 dogs and 32 cats) as well as cattle (17 reports) and horses (10 reports). Most of the reactions reported were linked to the use of antiparasitics (145 reports), hormone products (26 reports) and antiinfectives (10 reports). 32 reports were generated from consultations with Tox Info Suisse in Zürich and involved mainly the excessive intake of flavoured tablets and, in some cases, the use of reconverted products (applied to another species than that authorized). Five signals were identified from the reports, which resulted in revisions of the product information in the sections addressing contraindications or adverse reactions.

INTRODUCTION: En 2016, 253 annonces d'effets indésirables de médicaments vétérinaires ont été enregistrées, ce qui représente une diminution de 13% par rapport à l'année précédente (292 annonces). Ce sont principalement des annonces concernant des réactions chez les petits animaux (178 chiens et 32 chats) ainsi que chez les bovins (17) et les chevaux(10) qui ont été faites. Les groupes de médicaments les plus souvent impliqués étaient les antiparasitaires (145 annonces), les préparations hormonales (26) et les anti-infectieux (10). 32 cas transmis par Tox Info Suisse, concernaient principalement la prise en surdose de médicaments aromatisés ainsi que quelques reconversions. Cinq signaux issus de l'ensemble de ces annonces ont été identifiés, qui ont conduit à une adaptation des informations des produits concernés dans les rubriques "effets indésirables" ou "contre-indications".

[Vigilance of veterinary medicinal products: Reports of adverse reactions in the year 2014]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2014.

During the year 2014, a total of 268 adverse reactions due to Swissmedic-authorized veterinary medicinal products were reported representing an increase of 7% compared to the previous year. Similar to previous years, most of the reactions reported were linked to the use of antiparasitic products (47.8%) or antiinfectives (9.3%). In 10.8% of the reports, reactions were described after the use of products acting on the hormonal system. The affected animal species were primarily dogs (182 reports), cats (58 reports), and cattle (16 reports). Additionally, 33 reports were provided within the frame of consultations with the toxicological information centre in Zurich (Tox Info Suisse). We present a short overview of the safety of COX-2 inhibitors and a series of reactions following the use of a parenteral buprenorphine solution. Finally, the vaccinovigilance program received 124 declarations following the application of various vaccines, but no detailed analysis of those reports is available.

[Vigilance for veterinary medicinal products: reports of adverse reactions in the year 2012]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2012.

197 adverse reactions of Swissmedic-authorized veterinary medicinal products were reported during the year 2012 (2011: 167). Species and drug classes remain unchanged over the years: most of the reports related to reactions following the use of antiparasitic products (37.6 %), antiinfectives (15.7 %) or non-steroidal antiinflammatory drugs (11.7 %) in companion animals (94 dogs and 53 cats) followed by cattle/calves (29). Additionally, 45 cases transmitted by the Swiss Toxicological Information Centre in Zürich were processed. We discuss a paradoxical reaction under the potential influence of acepromazine as well as a modified protocol for treating permethrin intoxication in cats. Finally, the vaccinovigilance program received 95 declarations following the application of various vaccines, mainly to dogs or cats.

En 2012, on a enregistré 197 annonces de réactions après application de médicaments vétérinaires autorisés par Swissmedic (2011: 167). La répartition de ces annonces, tant en ce qui concerne les espèces que les classes de médicaments, est inchangée par rapport aux années précédentes: on a annoncé le plus souvent des réactions à des produits antiparasitaires (37.6 %), antiinfectieux (15.7 %) ou antiinflammatoires (11.7 %) chez les petits animaux (94 annonces concernaient des chiens, 53 des chats) suivis par les bovins (29 annonces). En outre 45 cas annoncés par le Centre suisse d'information toxicologique de Zürich dans le cadre de ses activités de conseil ont été étudiés. Une réaction paradoxale d'agressivité sous l'effet possible de l'acépromazine et un protocole modifié pour le traitement des intoxications à la perméthrine chez le chat sont présentés. Pour ce qui est de la vaccinovigilance effectuée par l'IVI, on a enregistré 95 annonces de réactions après l'application de divers vaccins, principalement chez des chiens et des chats.

[Vigilance for veterinary medicinal products: reports of adverse reactions in the year 2011]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2011.

167 adverse reactions of Swissmedic-authorized veterinary medicinal products were reported during the year 2011 (2010: 160). Species and drug classes remain comparable with previous years: most of the reactions occurred following the use of antiparasitic products (39 %), antiinfectives (20 %) or non-steroidal antiinflammatory drugs (11 %) in companion animals (85 dogs and 27 cats) followed by cattle/calves (37). We received 15 cases of adverse reactions following reconverted use, 8 of them in treated cats. Additionally the Swiss Toxicological Information Centre in Zürich processed 84 enquiries and transmitted them to Swissmedic. One case of a successful new therapy to treat ivermectin poisoning in a pony is presented. Finally, the vaccinovigilance program received 60 declarations following the application of various vaccines, mainly to dogs or cats.

[Vigilance for veterinary medicinal products: declarations of adverse reactions in the year 2010]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2010.

In 2010, we observed again an increase in the number of declarations reported to the vigilance system for veterinary medicinal products up to a total of 160. The species and drug classes reported remained the same as in previous years: the majority of adverse drug reactions (ADRs) concerned either dogs or cats and the most frequently involved drugs were either antiparasitic products or antiinfectives. Adverse reactions following reconversions and 8 cases of suspected allergic reactions following the use of amoxicillin-clavulanic acid combinations in dogs were reported. Additional enquiries were processed by the Swiss Toxicological Information Centre and transmitted to Swiss medic. 11 of these reported accidental ingestions of flavoured tablets in overdose by dogs and some cats. The vaccino vigilance program received 179 declarations following immunization against blue tongue disease as well as 82 declarations following the application of other vaccines. The vigilance system increases the chance to identify rare reactions or interactions and thereby contributes to the security of veterinary medicinal products.

[Vigilance for veterinary medicinal products: declarations of adverse reactions in the year 2009]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2009.

During the year 2009, 134 reports of suspected adverse drug reactions (ADRs) to veterinary medicinal products (VMPs) were received (106 in the year 2008). The distribution according to species and drug classes remained in line with previous years. Companion animals were involved in most of the reports (46 % dogs, 19 % cats), followed by cattle or calves (22 %). Antiparasitic drugs made the biggest part with 30 % of the reports, followed by antiinfectives (19 %) and hormones (13 %). Some reactions following their use are specifically discussed. 95 additional enquiries about ADRs of VMPs were received by the Swiss Toxicological Information Centre in Zürich. Most of them concerned dogs or cats and antiparasitics or anti-inflammatory drugs. In the vaccinovigilance program, a total of 1020 reports were received, of which 1000 were related to the vaccination against blue tongue disease. The most frequently reported adverse reactions were aborts, mastitis or alterations of milk quality and they are specifically discussed.

[Vigilance for veterinary medicinal products: declarations of suspected adverse reactions in the year 2007]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2007.

163 reports of suspected adverse reactions were received in the year 2007: 111 for veterinary medicinal (VMPs) and 52 for immunologic products. Half of the reported reactions for VMPs concerned either an antiparasitic drug (26%) or an antibiotic (24%). Reconversions (use in another target species or for another indication as registered) made the third most frequently mentioned group with 11 reports. For immunologicals, half of the declarations were related to an adverse reaction in dogs, the most frequently reported reaction in companion animals being allergies. Moreover, 272 enquiries were received by the Swiss Toxicological Information Center in Zürich. Most of these were related to dogs (73%) and the number of enquiries regarding VMPs correlated positively with the most frequently used therapeutic classes like antiparasitics (47%) and anti-inflammatory drugs (23%). The complexity of proscessing reports regarding the detection of residues in milk after prescribed withdrawal times is discussed in detail. In conclusion, the year 2007 is seen as a consolidation of the established system with a tendency towards increase in the number of complex cases.

[Drug interactions of phenylbutazone and phenprocoumon in a warmblood gelding]. / Arzneimittelinteraktionen von Phenylbutazon und Phenprocoumon bei einem Warmblutpferd.

A 15 year old Oldenburger gelding was treated during 3 weeks for laminitis with the anticoagulant phenprocoumone (27 mg orally, once daily) and concurrent administration of phenylbutazone (2-4 g orally, twice daily). After this treatment the animal was presented to the Equine Clinic University of Zurich with a history of acute colic and advanced symptoms of shock. On the basis of the clinical signs and laboratory values, a diagnosis of combined drug induced coagulopathy was made. The horse was treated with the antidote Vitamine-K1 (0.5 mg/kg, subcutaneously). Eventually, the general condition of the animal worsened and it was therefore euthanized. Necropsy revealed profound, multifocal hemorrhagic diathesis of the serosal surface of the viscera, as well as bleeding into the visceral cavities. This case shows that concurrent administration of phenprocoumone and phenylbutazone may lead to drug interactions that increase the anticoagulation effect of the coumarine-derivative. Simultaneous use of coumarine-derivatives and phenylbutazone is therefore contraindicated due to the higher risk of bleeding. A reasonable treatment of horses with anticoagulants requires regular monitoring with constant evaluation of coagulation status and special attention to potential drug interactions.

[Reported adverse reactions due to veterinary drugs in 2006]. / Gemeldete unerwünschte Wirkungen von Tierarzneimitteln im Jahr 2006.

We received 190 reports of suspected adverse events (SARs) following the use of veterinary drugs for the year 2006: 118 declarations for veterinary drugs and 72 declarations following the application of immunolgical medicinal products. Most of the 118 declarations relate to the use of antiparasitic drugs (48%) and every second declaration to drug use in dogs. Other drug classes concerned were, in decreasing order, antiinfectives (20%) and drugs used off-label (12%; other target species or other indication). For the vaccines, most of the reactions occurred in dogs (62%) followed by horses (11%) and cattle (10%). The most frequently reported reactions concerned the use of a vaccine against piroplasmosis. Another 349 requests for information were processed by the Swiss Toxicological Information center. We also present a case of a serious adverse reaction in form of a Stevens-Johnson syndrome in a cat as well as a case of ketamine abuse. We note the growing interest of practicing veterinarians with pleasure and are currently working on further adaptations to the system.

[Reported adverse reactions of veterinary drugs and vaccines in 2005]. / Gemeldete unerwünschte Wirkungen von Tierarzneimitteln im Jahr 2005.

We received 105 reports of suspected adverse events (SARs) following the use of veterinary drugs for the year 2005. This corresponds to a 35% increase compared to 2004. Practicing veterinarians sent most of these declarations. 73% of these concerned drugs used on companion animals. Antiparasitic drugs approved for topical use were the most frequently represented group with 48%, followed by drugs used to treat gastrointestinal disorders (11%) and drugs used off-label (14%; other target species or other indication). For the first time 2 declarations concerning the application of permethrin containing spot-on preparations used by mistake on cats were received. An overview of 20 declarations about adverse reactions following application of different vaccines is also presented with emphasis on the problem of fibrosarcoma in cats. We are pleased by the growing interest shown by practicing veterinarians for the vigilance system and hope to further develop this collaboration in the future.

[Suspected adverse drug reactions in 2004]. / Meldungen zu unerwünschten Wirkungen von Tierarzneimitteln im Jahr 2004.

We received 62 reports of suspected adverse events (SARs) for the year 2004. Their number and repartition according to affected animals and active substances were comparable with the previous year. The distributors or manufacturers submitted most of the declarations, but the proportion submitted by practicing veterinarians is slowly growing. 72% of the declarations dealt with adverse reactions in small animals (cats and dogs), followed by cattle and horses. Antiparasitics, anti-inflammatory drugs and immunologicals were the most frequently mentioned therapeutic classes, which are listed here according to the international ATCvet classification. A report from abroad about a fatality following injection of an antibiotic preparation for cattle prompted Swissmedic to review the security of this medication also sold on the Swiss market. It was decided to modify the package insert to warn about the danger of inadvertent self-injection in humans, to reduce the risk of similar accidents in Switzerland. We hope that the pharmacovigilance system will enjoy an increasing awareness by the practicing veterinarians.

[Pharmacovigilance for veterinary drugs in Switzerland]. / Pharmacovigilance für Tierarzneimittel in der Schweiz.

Pharmacovigilance is a system concerned with the acquisition, evaluation and classification of informations about suspected adverse drug reactions (SADR). Such a system was developed in Switzerland under the supervision of Swissmedic after the introduction of the federal law on therapeutic products on January 1st 2002. By sending declarations about SADRs, veterinary practitioners play a central role in this scheme. The reports are processed according to international standards (ABON) and provide useful hints to enhance the safety of drug usage by both patients and owners. The system acquired 58 reports in its first complete year of operation (2003). Analysis of these reveals that trends observed in foreign countries are also applicable to Switzerland: most of the reports concerned the use of antiparasitic or antibiotic drugs in small animals. The first year also revealed a high percentage of declarations coming from the pharmaceutical companies and the authors would therefore like to encourage practitioners to take a more active part in this scheme.

Poly ADP-ribosylation: a DNA break signal mechanism.

Recent evidence obtained with transgenic knockout mice suggests that the enzyme poly(ADP-ribose)polymerase (PARP) does not play a direct role in DNA break processing. Nevertheless, inactivation of the catalytic or the DNA nick-binding functions of PARP affects cellular responses to genotoxins at the level of cell survival, sister chromatid exchanges and apoptosis. In the present report, we conceptualize the idea that PARP is part of a DNA break signal mechanism. In vitro screening studies revealed the existence of a protein family containing a polymer-binding motif of about 22 amino acids. This motif is present in p53 protein as well as in MARCKS, a protein involved in the regulation of the actin cytoskeleton. Biochemical analyses showed that these sequences are directly targeted by PARP-associated polymers in vitro, and this alters several molecular functions of p53- and MARCKS protein. PARP-deficient knockout mice from transgenic mice were found to exhibit several phenotypic features compatible with altered DNA damage signaling, such as downregulation and lack of responsiveness of p53 protein to genotoxins, and morphological changes compatible with MARCKS-related cytoskeletal dysfunction. The knockout phenotype could be rescued by stable expression of the PARP gene. We propose that PARP-associated polymers may recruit signal proteins to sites of DNA breakage and reprogram their functions.