Lethal Treatment Research Articles

Gene transfer of cytidine deaminase protects myelopoiesis from cytidine analogs in an in vivo murine transplant model

AbstractHematopoietic stem cell gene transfer of the drug-resistance gene cytidine deaminase (CDD) protecting cells from the cytotoxic cytidine analogs cytarabine and gemcitabine was investigated in a murine transplant model. Following transplantation of CDD-transduced cells and cytarabine application (500 mg/kg; days 1-4; intraperitoneally) significant myeloprotection was demonstrated with nadir counts of peripheral blood granulocytes and thrombocytes of 2.9 ± 0.6/nL versus 0.7 ± 0.1/nL (P < .001) and 509 ± 147/nL versus 80 ± 9/nL (P = .008), respectively (CDD versus control). Protection also was observed from otherwise lethal gemcitabine treatment (250 mg/kg; days 1-3). Stable levels of gene-marked cells in primary and secondary recipients were demonstrated for up to 9 months, and whereas CDD overexpression clearly reduced B- and T-lymphocyte numbers, no major toxicity was observed in the myeloid compartment. Despite the profound myeloprotective properties, however, CDD overexpression did not allow for pharmacologic enrichment of transduced hematopoiesis in our model. Thus, in summary, our data establish CDD as a drug-resistance gene highly suitable for myeloprotective purposes, which, given the lack of selection observed in our hands, might best be used in combination with selectable drugresistance genes such as MGMT (P140K) or MDR1.

Israeli critical care nurses’ attitudes toward physician-assisted dying

Within critical care, end-of life decisions are common, including hastening of the dying process. One type of hastening the dying process is physician-assisted dying (PAD). The purpose of this study was to determine Israeli critical care nurses' attitudes and practices toward PAD. A convenience sample of 71 intensive care unit nurses were asked to fill out a modified critical care, Hebrew version of the Nurse's Attitudes Regarding Physician-Assisted Dying Questionnaire. Subjects were also asked whether they were requested or whether they performed actions to hasten the dying process. The majority of nurses supported PAD. However, only 10% of the respondents agreed to participate when PAD was to be administered by the nurse. Some nurses were asked by patients (12.7%) and/or by families (7.0%) to hasten the dying process. No nurse reported administering any lethal treatment. No significant differences in responses to the vignettes were found based on gender, marital status, place of birth or parents' place of birth, religion, age, type of education, having taken a post-basic course, years of general or intensive care unit nursing experience, or type of intensive care unit. However, significant differences were found in four vignettes based on level of self-perceived religiosity. The findings demonstrated that the Israeli critical care nurses sampled tended to agree with the concept of PAD but were unlikely to agree to having a more active role in hastening the dying process. This particular finding was true especially among those nurses who considered themselves more religious.

Roles of the cyanobacterial isiABC operon in protection from oxidative and heat stresses

The expression of the isiAB operon, which encodes CP43′ and flavodoxin, is induced under oxidative‐ or heat‐stress conditions as well as iron‐limited conditions. The aim of this study is to elucidate their roles for acquisition of tolerance by cells against oxidative or heat stress with using the isiA interruption and the isiB deletion mutants of Synechocystis sp. PCC 6803. In the former mutant, the isiA messenger RNA was truncated and the isiB transcription was totally abolished. Northern blot analysis indicated that an open reading frame sll0249 located immediate downstream of isiB is cotranscribed with isiAB under iron‐limited conditions. Thus, we designated the gene as isiC and constructed an isiC deletion mutant to test polar effects of the isiA and isiB disruptions on the isiC expression. All the mutants were highly sensitive to oxidative stress caused by the presence of methyl viologen, indicating an essential role of the operon, especially isiC, under oxidative stress. The isiA mutant was much more susceptible to the sublethal heat stress than the other mutants. Determination of the survival rate after a lethal temperature treatment confirmed the essential role of the isiA gene for the thermal stress management. We found that light conditions immediately after the lethal temperature treatment have a great effect on the survival rate of the wild‐type and the isiA mutant strains. We suggest that IsiA and IsiB may play a role in optimizing the light energy supply to avoid cellular damage and utilizing the light energy in the post‐heat‐stress recovery process.

Impact of malathion stress on lipid metabolism in Limnonectus limnocharis

Despite mounting concerns about amphibian population declines, information on impact of pesticides on physiological changes is meager. The present study deals the influence of an organophosphate pesticide—malathion on the lipid metabolism of Limnonectus limnocharis under laboratory conditions. Changes in the lipid metabolism were analyzed in the liver, muscle, ovary, and testis of frogs exposed to lethal (10.67 mg L −1 for 1, 2, 3, and 4 days) and sub-lethal (2.13 mg L −1 for 1, 5, 10, 15, 20, and 25 days) concentrations of malathion. Upon lethal concentration treatment, against the increase of fatty acids, glycerol, and lipase activities in all tested tissues, there was decrease in the total lipids content over different durations. On the other hand, exposure to sub-lethal concentration, the amount of total lipids content, free fatty acids, glycerol and lipase activity increased. Changes in the lipid metabolism due to lethal concentration of malathion exposure could depict the negative impact on the reproductive success, which would result in decline of amphibian population.

Factors Influencing Germination of Bacillus subtilis Spores via Activation of Nutrient Receptors by High Pressure

Different nutrient receptors varied in triggering germination of Bacillus subtilis spores with a pressure of 150 MPa, the GerA receptor being more responsive than the GerB receptor and even more responsive than the GerK receptor. This hierarchy in receptor responsiveness to pressure was the same as receptor responsiveness to a mixture of nutrients. The levels of nutrient receptors influenced rates of pressure germination, since the GerA receptor is more abundant than the GerB receptor and elevated levels of individual receptors increased spore germination by 150 MPa of pressure. However, GerB receptor variants with relaxed specificity for nutrient germinants responded as well as the GerA receptor to this pressure. Spores lacking dipicolinic acid did not germinate with this pressure, and pressure activation of the GerA receptor required covalent addition of diacylglycerol. However, pressure activation of the GerB and GerK receptors displayed only a partial (GerB) or no (GerK) diacylglycerylation requirement. These effects of receptor diacylglycerylation on pressure germination are similar to those on nutrient germination. Wild-type spores prepared at higher temperatures germinated more rapidly with a pressure of 150 MPa than spores prepared at lower temperatures; this was also true for spores with only one receptor, but receptor levels did not increase in spores made at higher temperatures. Changes in inner membrane unsaturated fatty acid levels, lethal treatment with oxidizing agents, or exposure to chemicals that inhibit nutrient germination had no major effect on spore germination by 150 MPa of pressure, except for strong inhibition by HgCl2.

Proline-directed protein kinase FA as a new signal transducing target for lethal cancer treatment

Proline-directed protein kinase F(A) (PDPK F(A)) has been established as a multisubstrate/multifunctional PDPK essential for the development of highly malignant phenotypes and rapid progression of lethal cancers. The recent immunohistochemical, immunocytochemical and clinicopathologic studies combined demonstrate that overexpressed PDPK F(A) is dynamically and closely associated with the most aggressive malignant cells disseminating from primary tumors to peripheral blood, ascites, pleural effusions and second metastatic tumors of various types of cancer patients with poor prognosis. The antisense gene therapeutic studies further demonstrate that overexpressed PDPK F(A) is essential for the development of all aspects of neoplasia including highly metastatic spread, peritoneal dissemination, splenomegaly and chemoradioresistances. The inhibition of cancer progression together with the simultaneous enhancement of chemoradiosensitivities through the suppression of overexpressed PDPK F(A) by specific drug design may work synergistically with surgery and chemoradiotherapy to improve the poor survival rate and life quality of the patients with lethal malignancies. PDPK F(A), therefore, may represent the heel of Achilles and a new promising target for the strategic development of more efficacious treatment for lethal cancers

Hematological Parameters of Tench (Tinca tinca L.) after Acute and Chronic Exposure to Lethal and Sublethal Mercury Treatments

Hematological Parameters of Tench (Tinca tinca L.) after Acute and Chronic Exposure to Lethal and Sublethal Mercury Treatments

Comparative analysis of the hspA mutant and wild-type Synechocystis sp. strain PCC 6803 under salt stress: evaluation of the role of hspA in salt-stress management.

DNA microarray analysis has previously revealed that hspA, which encodes a small heat-shock protein, is the second most highly expressed gene under salt stress in Synechocystis sp. strain PCC 6803. Consequently, an hspA deletion mutant was studied under various salt stresses in order to identify a potential role of HspA in salt stress management. The mutant had a growth disadvantage under moderate salt stress. It lost the ability to develop tolerance to a lethal salt treatment by a moderate salt pre-treatment when the tolerance was evaluated by cell survival and the level of major soluble proteins, phycocyanins, while the wild-type acquired tolerance. Under various salt stresses, the mutant failed to undergo the ultrastructural changes characteristic of wild-type cells. The mutant, which showed higher survival than the wild-type after a direct shift to lethal salt conditions, accumulated higher levels of groESL1 and groEL2 transcripts and the corresponding proteins, GroES, GroEL1, and GroEL2, suggesting a role for these heat-shock proteins in conferring basal salt tolerance. Under salt stress, heat-shock genes, such as hspA, groEL2, and dnaK2, were transcriptionally induced and greatly stabilized, indicating a transcriptional and post-transcriptional mechanism of acclimation to salt stress involving these heat-shock genes.

Treatment with oxidizing agents damages the inner membrane of spores of Bacillus subtilis and sensitizes spores to subsequent stress.

To determine if treatment of Bacillus subtilis spores with a variety of oxidizing agents causes damage to the spore's inner membrane. Spores of B. subtilis were killed 80-99% with wet heat or a variety of oxidizing agents, including betadine, chlorine dioxide, cumene hydroperoxide, hydrogen peroxide, Oxone, ozone, sodium hypochlorite and t-butylhydroperoxide, and the agents neutralized and/or removed. Survivors of spores pretreated with oxidizing agents exhibited increased sensitivity to killing by a normally minimal lethal heat treatment, while spores pretreated with wet heat did not. In addition, spores treated with wet heat or the oxidizing agents, except sodium hypochlorite, were more sensitive to high NaCl in plating media than were untreated spores. The core region of spores treated with at least two oxidizing agents was also penetrated much more readily by methylamine than was the core of untreated spores, and spores treated with oxidizing agents but not wet heat germinated faster with dodecylamine than did untreated spores. Spores of strains with very different levels of unsaturated fatty acids in their inner membrane exhibited essentially identical resistance to oxidizing agents. Treatment of spores with oxidizing agents has been suggested to cause damage to the spore's inner membrane, a membrane whose integrity is essential for spore viability. The sensitization of spores to killing by heat and to high salt after pretreatment with oxidizing agents is consistent with and supports this suggestion. Presumably mild pretreatment with oxidizing agents causes some damage to the spore's inner membrane. While this damage may not be lethal under normal conditions, the damaged inner membrane may be less able to maintain its integrity, when dormant spores are exposed to high temperature or when germinated spores are faced with osmotic stress. Triggering of spore germination by dodecylamine likely involves action by this agent on the spore's inner membrane allowing release of the spore core's depot of dipicolinic acid. Presumably dodecylamine more readily alters the permeability of a damaged inner membrane and thus more readily triggers germination of spores pretreated with oxidizing agents. Damage to the inner spore membrane by oxidizing agents is also consistent with the more rapid penetration of methylamine into the core of treated spores, as the inner membrane is likely the crucial permeability barrier to methylamine entry into the spore core. As spores of strains with very different levels of unsaturated fatty acids in their inner membrane exhibited essentially identical resistance to oxidizing agents, it is not through oxidation of unsaturated fatty acids that oxidizing agents kill and/or damage spores. Perhaps these agents work by causing oxidative damage to key proteins in the spore's inner membrane. The more rapid heat killing and germination with dodecylamine, the greater permeability of the spore core and the osmotic stress sensitivity in outgrowth of spores pretreated with oxidizing agents is consistent with such agents causing damage to the spore's inner membrane, even if this damage is not lethal under normal conditions. It may be possible to take advantage of this phenomenon to devise improved, less costly regimens for spore inactivation.

Stationary-phase acid and heat treatments for improvement of the viability of probiotic lactobacilli and bifidobacteria.

To investigate whether sublethal treatments of stationary-phase probiotic cultures enhance their survival during lethal treatments and to adapt these treatments to the fermenter-scale production of probiotic cultures. Conditions for acid and heat pretreatments were screened for three Lactobacillus and two Bifidobacterium strains. Strains were sublethally treated both at laboratory scale and at fermenter scale in a strain-specific manner and exposed to a subsequent lethal treatment. At laboratory scale viability improvement was detected in each strain. However, improvement was more pronounced in the Lactobacillus than in the Bifidobacterium strains. At fermenter scale three strains were tested: for the two Lactobacillus strains a marked improvement in viability was obtained whereas for the Bifidobacterium strain the improvement was either minor or not detected. Development of treatments for viability enhancement of probiotic strains is feasible, but strain-specific optimization is necessary to obtain notable improvements. Strain-specific treatments were developed for the viability enhancement of stationary-phase probiotic cells both at laboratory and fermenter scale. These results can be utilised in the production of probiotic cultures with improved viability.

Protective effect of sucrose and sodium chloride for Lactococcus lactis during sublethal and lethal high-pressure treatments.

The bactericidal effect of hydrostatic pressure is reduced when bacteria are suspended in media with high osmolarity. To elucidate mechanisms responsible for the baroprotective effect of ionic and nonionic solutes, Lactococcus lactis was treated with pressures ranging from 200 to 600 MPa in a low-osmolarity buffer or with buffer containing 0.5 M sucrose or 4 M NaCl. Pressure-treated cells were characterized in order to determine viability, the transmembrane difference in pH (DeltapH), and multiple-drug-resistance (MDR) transport activity. Furthermore, pressure effects on the intracellular pH and the fluidity of the membrane were determined during pressure treatment. In the presence of external sucrose and NaCl, high intracellular levels of sucrose and lactose, respectively, were accumulated by L. lactis; 4 M NaCl and, to a lesser extent, 0.5 M sucrose provided protection against pressure-induced cell death. The transmembrane DeltapH was reversibly dissipated during pressure treatment in any buffer system. Sucrose but not NaCl prevented the irreversible inactivation of enzymes involved in pH homeostasis and MDR transport activity. In the presence 0.5 M sucrose or 4 M NaCl, the fluidity of the cytoplasmic membrane was maintained even at low temperatures and high pressure. These results indicate that disaccharides protect microorganisms against pressure-induced inactivation of vital cellular components. The protective effect of ionic solutes relies on the intracellular accumulation of compatible solutes as a response to the osmotic stress. Thus, ionic solutes provide only asymmetric protection, and baroprotection with ionic solutes requires higher concentrations of the osmolytes than of disaccharides.

Oxidative damage to proteins in yeast cells exposed to adaptive levels of H2O2

When yeast cells are exposed to sublethal concentrations of oxidants, they adapt to tolerate subsequent lethal treatments. Here, we show that this adaptation involves tolerance of oxidative damage, rather than protection of cellular constituents. o- and m-tyrosine levels are used as a sensitive measure of protein oxidative damage and we show that such damage accumulates in yeast cells exposed to H2O2 at low adaptive levels. Glutathione represents one of the main cellular protections against free radical attack and has a role in adaptation to oxidative stress. Yeast mutants defective in glutathione metabolism are shown to accumulate significant levels of o- and m-tyrosine during normal aerobic growth conditions.

Susceptibility and adaptive response to bile salts in Propionibacterium freudenreichii: physiological and proteomic analysis.

Tolerance to digestive stresses is one of the main factors limiting the use of microorganisms as live probiotic agents. Susceptibility to bile salts and tolerance acquisition in the probiotic strain Propionibacterium freudenreichii SI41 were characterized. We showed that pretreatment with a moderate concentration of bile salts (0.2 g/liter) greatly increased its survival during a subsequent lethal challenge (1.0 g/liter, 60 s). Bile salts challenge led to drastic morphological changes, consistent with intracellular material leakage, for nonadapted cells but not for preexposed ones. Moreover, the physiological state of the cells during lethal treatment played an important role in the response to bile salts, as stationary-phase bacteria appeared much less sensitive than exponentially growing cells. Either thermal or detergent pretreatment conferred significantly increased protection toward bile salts challenge. In contrast, some other heterologous pretreatments (hypothermic and hyperosmotic) had no effect on tolerance to bile salts, while acid pretreatment even might have sensitized the cells. Two-dimensional electrophoresis experiments revealed that at least 24 proteins were induced during bile salts adaptation. Identification of these polypeptides suggested that the bile salts stress response involves signal sensing and transduction, a general stress response (also triggered by thermal denaturation, oxidative toxicity, and DNA damage), and an alternative sigma factor. Taken together, our results provide new insights into the tolerance of P. freudenreichii to bile salts, which must be taken into consideration for the use of probiotic strains and the improvement of technological processes.

Role of Listeria monocytogenes sigma(B) in survival of lethal acidic conditions and in the acquired acid tolerance response.

The food-borne pathogen Listeria monocytogenes can acquire enhanced resistance to lethal acid conditions through multiple mechanisms. We investigated contributions of the stress-responsive alternative sigma factor, sigma(B), which is encoded by sigB, to growth phase-dependent acid resistance (AR) and to the adaptive acid tolerance response in L. monocytogenes. At various points throughout growth, we compared the relative survival of L. monocytogenes wild-type and DeltasigB strains that had been exposed to either brain heart infusion (pH 2.5) or synthetic gastric fluid (pH 2.5) with and without prior acid adaptation. Under these conditions, survival of the DeltasigB strain was consistently lower than that of the wild-type strain throughout all phases of growth, ranging from 4 orders of magnitude less in mid-log phase to 2 orders of magnitude less in stationary phase. Survival of both DeltasigB and wild-type L. monocytogenes strains increased by 6 orders of magnitude upon entry into stationary phase, demonstrating that the L. monocytogenes growth phase-dependent AR mechanism is sigma(B) independent. sigma(B)-mediated contributions to acquired acid tolerance appear to be greatest in early logarithmic growth. Loss of a functional sigma(B) reduced the survival of L. monocytogenes at pH 2.5 to a greater extent in the presence of organic acid (100 mM acetic acid) than in the presence of inorganic acid alone (HCl), suggesting that L. monocytogenes protection against organic and inorganic acid may be mediated through different mechanisms. sigma(B) does not appear to contribute to pH(i) homeostasis through regulation of net proton movement across the cell membrane or by regulation of pH(i) buffering by the GAD system under the conditions examined in this study. In summary, a functional sigma(B) protein is necessary for full resistance of L. monocytogenes to lethal acid treatments.

Molecular characterization of Enterococcus faecalis two-component signal transduction pathways related to environmental stresses.

A key issue in the comprehension of the Enterococcus faecalis stress response is to understand how this bacterium is able to modulate its gene expression in accordance to environmental conditions. Through bioinformatic analysis of the E. faecalis V583 genome, nine two-component systems and a single orphan response regulator were identified. A transcriptional study gave evidence of four systems whose expression is induced by at least one environmental stress. In addition, gene disruption experiments allowed the isolation of eight response regulator mutants. Insertional inactivation of the response regulator gene err 05 resulted in growth default and cell morphology alterations; and also in expression default of the sagA gene, this latter being recently shown involved in E. faecalis stress resistance toward numerous lethal treatments (Y. Le Breton, A. Mazé, A. Hartke, S. Lemarinier, Y. Auffray and A. Rincé (2002) Current Microbiol 45: 434-439). Disruption of the err 04, err 08 or err 18 genes resulted in sensitivity towards heat. Finally, the err 10 mutant was shown to be more sensitive to acid pH and NaCl whereas its growth was less affected by bile salts or heat. We also demonstrated that the heat resistance phenotype of the err 10 mutant was correlated with an increase of the heat shock proteins DnaK and GroEL level.

Changes in heat shock protein 27 phosphorylation and immunocontent in response to preconditioning to oxygen and glucose deprivation in organotypic hippocampal cultures

Organotypic hippocampal cultures have been recently used to study in vitro ischaemic neuronal death. Sub-lethal periods of ischaemia in vivo confer resistance to lethal insults and many studies have demonstrated the involvement of heat shock proteins in this phenomenon. We used organotypic hippocampal cultures to investigate the involvement of heat shock protein (HSP) 27 in preconditioning to oxygen and glucose deprivation. Neuronal damage was assessed using propidium iodide fluorescence; HSP27 phosphorylation and immunocontent were obtained using 32Pi labelling followed by sodium dodecylsulfate-polyacrylamide gel electrophoresis and immunoblotting. We observed that immunocontent of HSP27 was increased after lethal or sub-lethal treatment, indicating it is a response to metabolic stress. Treatments with 5 or 10 min of oxygen and glucose deprivation (OGD) or 1-μM N-methyl- d-aspartate (NMDA) induced tolerance to 40 min of OGD associated with an increase in HSP27 immunocontent and phosphorylation. These data suggest that, in vitro, phosphorylated HSP27 might be involved in preconditioning, probably acting as a modulator of actin filaments or by the blockage of neurodegenerative processes.

Viability and maturation of Aphanomyces cochlioides oospores

Plasmolysis, tetrazolium bromide staining and microscopic appearance were tested for their usefulness in determining viability of oospores of Aphanomyces cochlioides. For comparison, three lethal treatments were employed to contrast the reaction of dead oospores and untreated, presumably viable oospores. Few oospores stained with tetrazolium bromide, even though plasmolysis and microscopic appearance indicated that 85% were viable. Cytoplasm of viable oospores was densely organized and uniformly granular (DOUG), whereas cytoplasm of oospores exposed to lethal treatments was loosely organized and non-uniformly granular (LONG). Dose-response bioassay experiments were conducted with untreated oospores of varying inoculum densities or with mixtures of untreated DOUG and heat-treated LONG oospores in varying proportions. The number of DOUG oospores was correlated (R2 = 0.62, P < 0.001) with severity of damping-off of sugar beet seedlings caused by A. cochlioides. Thus, the granular appearance of cytoplasm offered a fast, easy and reliable indicator of viability of A. cochlioides oospores. Tests with newly formed oospores/oogonia showed that >80% harvested at 3–4 d after inoculation of hypocotyls stained with tetrazolium, but by 8–9 d <10% stained, apparently because of declining permeability of the spore wall to tetrazolium as oospores matured.

Viability and Maturation of Aphanomyces cochlioides Oospores

Plasmolysis, tetrazolium bromide staining and microscopic appearance were tested for their usefulness in determining viability of oospores of Aphanomyces cochlioides. For comparison, three lethal treatments were employed to contrast the reaction of dead oospores and untreated, presumably viable oospores. Few oospores stained with tetrazolium bromide, even though plasmolysis and microscopic appearance indicated that 85% were viable. Cytoplasm of viable oospores was densely organized and uniformly granular (DOUG), whereas cytoplasm of oospores exposed to lethal treatments was loosely organized and non-uniformly granular (LONG). Dose-response bioassay experiments were conducted with untreated oospores of varying inoculum densities or with mixtures of untreated DOUG and heat-treated LONG oospores in varying proportions. The number of DOUG oospores was correlated (R2 = 0.62, P < 0.001) with severity of damping-off of sugar beet seedlings caused by A. cochlioides. Thus, the granular appearance of cytoplasm offered a fast, easy and reliable indicator of viability of A. cochlioides oospores. Tests with newly formed oospores/oogonia showed that >80% harvested at 3–4 d after inoculation of hypocotyls stained with tetrazolium, but by 8–9 d <10% stained, apparently because of declining permeability of the spore wall to tetrazolium as oospores matured.

Genetic variation in drought tolerance in picea abies seedlings and its relationship to growth in controlled and field environments

Drought tolerance, phenology, height‐growth and biomass were studied in 36 open‐pollinated Picea abies families in a growth chamber over two growth periods. Three different irrigation treatments were applied: well‐watered, periodic drought and lethal drought (involving watering during the first growth period and withholding water during the second). The periodic drought treatment yielded significantly smaller seedlings than the well‐watered treatment. In the lethal drought treatment 5.6% of the seedlings were still alive after 3 months without irrigation. Heritabilities for drought damage score, days to wilting and days to necrosis in the lethal drought treatment were 0.41, 0.23 and 0.20, respectively. Additive genetic correlation estimates between drought tolerance traits and growth traits in the growth chamber treatments and in four field progeny trials were weak and mainly non‐significant. High drought tolerance was correlated with early budset and, to a lower extent, late budburst. In conclusion, selection for height growth and late budburst as practised in Swedish breeding and propagation populations is not likely to reduce seedling drought tolerance.

Genetic Variation in Drought Tolerance in Picea abies Seedlings and its Relationship to Growth in Controlled and Field Environments

Drought tolerance, phenology, height‐growth and biomass were studied in 36 open‐pollinated Picea abies families in a growth chamber over two growth periods. Three different irrigation treatments were applied: well‐watered, periodic drought and lethal drought (involving watering during the first growth period and withholding water during the second). The periodic drought treatment yielded significantly smaller seedlings than the well‐watered treatment. In the lethal drought treatment 5.6% of the seedlings were still alive after 3 months without irrigation. Heritabilities for drought damage score, days to wilting and days to necrosis in the lethal drought treatment were 0.41, 0.23 and 0.20, respectively. Additive genetic correlation estimates between drought tolerance traits and growth traits in the growth chamber treatments and in four field progeny trials were weak and mainly non‐significant. High drought tolerance was correlated with early budset and, to a lower extent, late budburst. In conclusion, selection for height growth and late budburst as practised in Swedish breeding and propagation populations is not likely to reduce seedling drought tolerance.