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Doxorubicin sensitivity pattern in a panel of small-cell lung-cancer cell lines: correlation to etoposide and vincristine sensitivity and inverse correlation to carmustine sensitivity.

The aim of our investigations is to evaluate whether the sensitivity patterns of small-cell lung-cancer (SCLC) cell lines in vitro can be used in evaluating new drugs and in selecting drugs for the optimization of combination therapy. In our attempts to obtain a panel of cell lines demonstrating differential patterns in sensitivity, we have developed three SCLC lines exhibiting different types of multidrug resistance (MDR). In the present investigations we compared the sensitivity patterns shown by five wild-type SCLC lines and three MDR lines in response to six different types of drugs: doxorubicin, cytarabine, carmustine, cisplatin, vincristine, and etoposide. In the wild-type SCLC cell lines, the range of variation in sensitivity to all drugs was within a factor of 10. Cell lines showing low sensitivity to doxorubicin also exhibited low sensitivity to etoposide and vincristine, and vice versa. In contrast, the pattern of sensitivity to carmustine was almost the opposite of that to doxorubicin. A tendency to an inverse relationship between doxorubicin and carmustine sensitivity was also observed when doxorubicin sensitivity was reduced in near stationary cells and in cells exposed to the metabolic inhibitor 2-deoxy-D-glucose. In agreement with the pattern observed for the wild-type lines, all of the MDR sublines demonstrated collateral sensitivity to carmustine. As to cytarabine, the wild-type lines expressed a sensitivity pattern similar to that shown in response to doxorubicin. Interestingly, the opposite pattern was found in the MDR lines, as all three demonstrated cytarabine hypersensitivity. The combination of alkylating agents and "MDR" drugs are of proven clinical benefit in the treatment of solid tumors, as is the combination of anthracycline and cytarabine in acute myeloid leukemia. The experimentally derived sensitivity data on cytarabine, alkylating agents, and MDR drugs (i.e., etoposide, doxorubicin, vincristine) thus resemble the clinical experience with these drugs, and we conclude that the use of a clonogenic assay on the described panel of SCLC cell lines can give valuable information for the selection of agents for combination therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem

Predictive value of the analogy between hormone-sensitive adenylate cyclase and light-sensitive photoreceptor cyclic GMP phosphodiesterase: a specific role for a light-sensitive GTPase as a component in the activation sequence.

We report experiments which involve a light sensitive GTPase in the light dependent activation of retinal rod 3'5'-cyclic guanosine monophosphate (cGMP) phosphodiesterase (PDE). The data suggest that the light activated GTPase is intermediate between rhodopsin and PDE in the light-dependent activation sequence. We list the many striking similarities between hormone sensitive adenylate cyclase and light activated PDE in order to emphasize that the findings presented herein may have predictive value for ongoing studies of the hormone sensitive adenylate cyclase specifically regarding the role of the hormone activated GTPase in the activation sequence.

3',5'-Cyclic-GMP Phosphodiesterases

Milk sensitivity and soybean sensitivity in the production of eczematous manifestations in breast-fed infants with particular reference to intrauterine sensitization.

Three cases of milk sensitivity and two of soybean sensitivity are presented, suggesting that both pre-natal and post-natal sensitization may have been involved in the production of eczematous manifestations of early infancy. Hemagglutinating antibody titers against lactalbumin and soybean in the amniotic fluid were unusually high. This suggests that hemagglutinating antibody estimation against foods in the amniotic fluid may possibly predict infantile allegic manifestations in the newborn.

Adult

Comparative studies of wild-type and cold-mutant (temperature-sensitive) influenza viruses: independent segregation of temperature-sensitivity of virus replication from temperature-sensitivity of virion transcriptase activity during recombination of mutant A/Ann Arbor/6/60 with wild-type H3N2 strains.

RNA 1 (see end of Summary) of a cold-adapted and temperature-sensitive (ts) influenza virus mutant A/Ann Arbor/6/60 has a different mobility from RNA 1 of wild-type (wt) A/Ann Arbor/6/60 when subjected to electrophoresis through acrylamide/agarose gels in the absence of denaturing agents. Detection of this lesion in RNA 1 of the mutant virus was dependent on the temperature of the gel during electrophoresis. Because RNA 1 is believed to code for a protein involved in virus-specific RNA synthesis we compared phenotypes of virion transcriptases in the wt and mutant viruses. The enzyme of the mutant virus was found to be about 40% less active at 40 degrees C than the enzyme of the wt virus when related to their activities at 31 degrees C. Two cold-adapted ts recombinants which derive their RNA 1 from the mutant A/Ann Arbor/6/60 have virion transcriptases with a phenotype similar to that of their mutant parent. Three different cold-adapted ts recombinants, however, which also derive their RNA 1 from the mutant A/Ann Arbor/6/60, have virion transcriptases with a phenotype similar to that of wt virus. We conclude, therefore, that the conditional-lethal ts property of A/Ann Arbor/6/60 mutant and its recombinants is independent of the phenotypic marker observed for the A/Ann Arbor/6/60 mutant virion transcriptase, and that the lesion in RNA 1 of the mutant may also be unrelated to the observed difference between virion transcriptases of the mutant and wt A/Ann Arbor/6/60 viruses. The phenotypes of the virion transcriptases in recombinants did, however, correlate with the derivation of their RNA 2. This suggests that the increased temperature-sensitivity of virion transcriptase of the A/Ann Arbor/6/60 mutant is caused by either (1) a lesion (not necessarily conditionally lethal) that occurred in its RNA 2 during the course of cold-adaptation, or (2) a lesion in another gene whose product is a component of the virion transcriptase complex, but which lesion is only expressed phenotypically when there is a synergistic interaction in the transcriptase complex with the product of A/Ann Arbor/6/60 rna 2.

Cold Temperature

Food sensitivity reported by patients with asthma and hay fever. A relationship between food sensitivity and birch pollen-allergy and between food sensitivity and acetylsalicylic acid intolerance.

Among adult patients with bronchial asthma and/or allergic rhinitis undergoing allergological investigation with skin test, nasal provocation test and RAST, 1129 answered a questionaire regarding food sensitivity (FS). 276 (24%) of the patients reported some kind of allergic symptoms on eating or handling various foods, of which hazel nut, apple and shell fish were the most often named. Females reported FS more often than males. A correlation was found between birch pollen allergy and FS with nuts, apple, peach, cherry, pear, plum, carrot and new potato. The higher the degree of birch pollen allergy, according to skin test, RAST or provocation test, the higher the frequency of FS. A correlation was found too between acetylsalicylic acid intolerance and FS with some foods, e.g. nuts, strawberry, almond, green pepper, hip, chocolate, egg, cabbage, milk and wine. The connection between birch pollen allergy and FS is probably explained by the structural relationship between birch pollen allergen and some allergens of the foodstuffs, whereas the high incidence of FS in acetylsalicylic acid-intolerant patients is probably explained by additives in foods as well as salicylates or benzoates naturally occurring in some food.

Adolescent

The migratory behavior of T blasts to contact sensitivity reactions in activelyand passively sensitized mice.

The arrival of cells from lymph nodes immunized with the contact sensitizing agents oxazolone and picryl chloride at ears challenged with these antigens was studied inmice using the technique of labelling with -51Cr. An apparent specificity of arrival was seen because the immune cells transfered contact sensitivity passively, giving rise to an inflammatory response in the ear, to which a subpopulation of cells (T blasts) was non-specifically attracted. It was also shown that there are at least two distinct populations of cells with the ability to move to inflammatory sites: the first, found in immunized lymph nodes, moves to contact sensitivity reactions in both actively and passively sensitized mice; the second, found in bone marrow and oil-induced peritoneal exudates, moves to contact sensitivity reactions in actively sensitized mice, whereas in passively sensitized mice, the arrival of these cells at contact sensitivity reaction is poor. It is suggested that the ability of T blasts to move to sites of inflammation my be useful as an assay technique for contact sensitivity reactions.

Animals

[Comparative studies on the sensitivity of smooth bronchial muscles to catecholamines during sensitization with various allergens].

An attempt has been made to compare the effects produced by adrenergic agents on smooth bronchial muscles of normal and BCG- as well as ovalbumin-sensitized guinea pigs. The method of determining the state of relaxation of the isolated bronchial tree was used to ascertain the degree of sensitivity to adrenergic agents of smooth bronchial muscles. Experiments conducted on a total of 34 guinea pigs showed a considerable decrease in the response of smooth bronchial muscles to novodrine, adrenaline, and noradrenaline subsequent to BCG and ovalbumin sensitization of experimental animals. In normal guinea pigs, minimal relaxation of smooth tracheal muscles was brought about by 7.10(-8) - 1.10(-7) G/ml novodrine, 1.10(-7) - 9.10(-7) g/ml adrenaline, and 1.10(-6) - 8.10(-6) g/ml noradrenaline. For BCG-sensitized animals, the data obtained were 3.10(-7) - these agents of smooth bronchial muscles of guinea pigs was more clearly evident in BCG-sensitized 2.10(-6) g/ml, 1.10(-6) - 2.10(-6) g/ml, and 3.10(-6) - 6.10(-6) g/ml, respectively. The decrease in sensitivity to bronchi during the process of sensitization is believed to be responsible for the decrease in response to animals than in ovalbumin-sensitized guinea pigs. A partial blockade of beta-adrenergic receptors of catecholamines. The degree of partial blockade is dependent upon the kind of sensitization.

Allergens

[Platelet activating factor (PAF)-induced late asthmatic response in sensitized but not in non-sensitized guinea pigs].

We have recently demonstrated that pretreatment with WEB 2086, a specific PAF antagonist or cyclosporine A (CsA), a potent helper T cell suppressant, resulted in preventing the development of late asthmatic response (LAR) and increase of airway hyperreactivity (AH) in guinea pig experimental models of asthma. We have now examined whether exogenously applied PAF causes LAR in these models in vivo. The respiratory resistance (Rrs) of guinea pigs was measured by an oscillation technique and histological studies of the bronchi were also made. Guinea pigs, actively sensitized by repeated antigen (ovalbumin; OA) inhalation, showed a leftward shift of the inhaled PAF dose response curve of Rrs compared with that in control animals, indicating that the sensitized animals were more sensitive to inhaled, PAF. PC200 PAF, which indicate provocative concentrations of PAF aerosols causing a 200% increase in the baseline Rrs, were 3800 +/- 604.9 micrograms/ml and 780 +/- 94.3 micrograms/ml, in the control and sensitized animals, respectively. The same magnitude of immediate bronchoconstriction after 780 and 3800 micrograms/ml of PAF exposure was observed in the actively sensitized and non-sensitized control animals, respectively. However, LAR developed 4 out of 6 animals only in the sensitized guinea pigs. We conclude that both exogenously applied PAF by inhalation and antigen exposure are capable of inducing LAR in sensitized guinea pigs, and thus the priming effect of immunization and PAF may contribute to the development of LAR observed in asthma.

Airway Resistance

Immune suppression with supraoptimal doses of antigen in contact sensitivity. I. Demonstration of suppressor cells and their sensitivity to cyclophosphamide.

Immunologic suppression was induced in a mouse model of contact sensitization to DNFB by using supraoptimal doses of antigen. In these studies, in vivo measurement of ear swelling as an indication of immunologic responsiveness correlated well with measurement of in vitro antigen-induced cell proliferation. This unresponsiveness was specific, since supraoptimal doses of DNFB did not interfere with the development of contact sensitivity to another contactant, oxazolone. The decrease in responsiveness is a form of active suppression, as lymphoid cells from supraoptimally sensitized donors transferred suppression to normal recipients. Furthermore, pretreatment with cyclophosphamide (Cy) reversed the suppression seen in supraoptimally sensitized animals but had no effect on the optimal sensitization regimen. These results indicate that supraoptimal doses of contactants can activate suppressor cells and that precursors of these cells are sensitive to Cy. Such suppressors regenerate within 7 to 14 days after Cy treatment. The ability of Cy pretreatment to affect supraoptimal sensitization without affecting optimal sensitization confirms other reports indicating that the observed results of Cy treatment depend critically upon the dose of antigen used.

Animals

Herpes simplex virus DNA polymerase as the site of phosphonoacetate sensitivity: temperature-sensitive mutants.

Temperature-sensitive (ts) mutants in a number of complementation groups of herpes simplex virus type 1 (HSV-1) are deficient in DNA polymerase induction at the restrictive temperature. Twenty-two mutants in 15 complementation groups were tested for sensitivity to phosphonoacetate (PAA), a compound that inhibits HSV replication in vivo and the DNA polymerase in vitro. One mutant, tsD9, was resistant to PAA (Pr), whereas all others were sensitive. Revertants of tsD9 to the ts+ phenotype simultaneously lost PAA resistance. Additional Pr mutants were isolated from ts mutants belonging to several complementation groups of HSV-1. Double mutants (ts Pr phenotype) were used in three-factor recombination analyses to locate the PAA locus on the genetic map at a position indistinguishable from the ts lesion in tsD9. In all cases, resistance or sensitivity to PAA in vivo was correlated with resistance or sensitivity of DNA polymerase in vitro. These data are compatible with the temperature-sensitive lesion of tsD9 and the determinant of PAA sensitivity both residing in the structural gene for DNA polymerase.

DNA-Directed DNA Polymerase

Establishment of human squamous carcinoma cell lines highly and minimally sensitive to bleomycin and analysis of factors involved in the sensitivity.

Human squamous carcinoma cell lines that were highly and minimally sensitive to bleomycin were established from clinical specimens and designated as SCCKN and SCCTF, respectively. Although these cell lines showed a similar growth doubling time in vitro, SCCTF was approximately ten times less sensitive to bleomycin than SCCKN. The bleomycin high and low sensitivities were stable even at the 70-cell passage level in vitro. In addition, nude mouse tumors produced by SCCTF were less sensitive to bleomycin that those produced by SCCKN, and the ratio of the mean tumor weight in bleomycin-treated mice to that in control mice was 89.2% in SCCTF and 18.8% in SCCKN. As compared with SCCKN, SCCTF also was less sensitive to peplomycin (5-fold), mitomycin C (2.3-fold), cis-diamine dichloroplatinum (2.5-fold), and vincristine (6.5-fold). Analyses of low bleomycin sensitivity showed that SCCTF had an approximately 20% decreased cellular accumulation and retention of bleomycin, 1.2-fold increase of bleomycin hydrolase activity, elevated DNA repair activity, and increased poly(adenosine diphosphate-ribose) polymerase activity as compared with SCCKN.

Animals

Rapid chloroquine efflux phenotype in both chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum. A correlation of chloroquine sensitivity with energy-dependent drug accumulation.

Recent reports suggest that lower levels of chloroquine accumulation in chloroquine-resistant isolates of Plasmodium falciparum are achieved by energy-dependent chloroquine efflux from resistant parasites. In support of this argument, a rapid chloroquine efflux phenotype has been observed in some chloroquine-resistant isolates of P. falciparum. In this study, no relationship was found between chloroquine sensitivity and the rate of [3H]chloroquine efflux from four isolates of P. falciparum with a greater than 10-fold range in sensitivity to chloroquine. All the isolates tested displayed the rapid efflux phenotype, irrespective of sensitivity. However, chloroquine sensitivity of these isolates was correlated with energy-dependent rate of drug accumulation into these parasites. Verapamil and a variety of other compounds reverse chloroquine resistance. The reversal mechanism is assumed to result from competition between verapamil and chloroquine for efflux protein translocation sites, thus causing an increase in steady-state accumulation of chloroquine and hence a return to sensitivity. Verapamil accumulation at a steady-state is increased by chloroquine, possibly indicating competition for efflux of the two substrates. Increases in steady-state verapamil concentrations caused by chloroquine were identical in sensitive and resistant strains, suggesting that similar capacity efflux pumps may exist in these isolates. These data suggest that differences in steady-state chloroquine accumulation seen in these isolates can be attributed to changes in the chloroquine concentrating mechanism rather than the efflux pump. It seems likely that chloroquine resistance generally in P. falciparum, results at least in part from a change in the drug concentrating mechanism and that changes in efflux rates per se are insufficient to explain chloroquine resistance.

Animals

Voltage-sensitive and solvent-sensitive processes in ion channel gating. Kinetic effects of hyperosmolar media on activation and deactivation of sodium channels.

Kinetic effects of osmotic stress on sodium ionic and gating currents have been studied in crayfish giant axons after removal of fast inactivation with chloramine-T. Internal perfusion with media made hyperosmolar by addition of formamide or sucrose, reduces peak sodium current (before and after removal of fast inactivation with chloramine-T), increases the half-time for activation, but has no effect on tail current deactivation rate(s). Kinetics of ON and OFF gating currents are not affected by osmotic stress. These results confirm (and extend to sodium channels) the separation of channel gating mechanisms into voltage-sensitive and solvent-sensitive processes recently proposed by Zimmerberg J., F. Bezanilla, and V. A. Parsegian. (1990. Biophys. J. 57:1049-1064) for potassium delayed rectifier channels. Additionally, the kinetic effects produced by hyperosmolar media seem qualitatively similar to the kinetic effects of heavy water substitution in crayfish axons (Alicata, D. A., M. D. Rayner, and J. G. Starkus. 1990. Biophys. J. 57:745-758). However, our observations are incompatible with models in which voltage-sensitive and solvent-sensitive gating processes are presumed to be either (a) strictly sequential or, (b) parallel and independent. We introduce a variant of the parallel model which includes explicit coupling between voltage-sensitive and solvent-sensitive processes. Simulations of this model, in which the total coupling energy is as small as 1/10th of kT, demonstrate the characteristic kinetic changes noted in our data.

Animals

Glucose intolerance in uremia. Quantification of pancreatic beta cell sensitivity to glucose and tissue sensitivity to insulin.

The relative contributions of impaired insulin secretion and of tissue insensitivity to insulin to the carbohydrate intolerance of uremia were investigated in 10 chronically uremic subjects. Two types of glucose-clamp experiments were performed in each patient before and after 10 wk of thrice weekly hemodialysis. In both types the blood glucose concentration was maintained at a constant level by the periodic adjustment of a variable glucose infusion with a negative feedback formula.Hyperglycemic clamp. The blood glucose concentration was acutely raised and maintained 125 mg/dl above basal levels for 2 h. Since the glucose concentration was held constant, the glucose infusion rate is an index of glucose metabolism (M). After dialysis M increased in all patients from an average of 4.23 to 6.30 mg/kg body wt per min (P < 0.001). The plasma insulin responses (I) both pre- and postdialysis were biphasic with an early burst within the first 2-5 min, followed by a phase of gradually increasing insulin concentration. After dialysis the plasma insulin response diminished slightly. Consequently, the M/I ratio, an index of tissue sensitivity to endogenous insulin, increased postdialysis in all subjects by an average of 92% (P < 0.01). Euglycemic clamp. The plasma insulin concentration was acutely raised and maintained by a primecontinuous insulin infusion. The blood glucose concentration was held constant at the basal level by a variable glucose infusion as above. M/I again is a measure of tissue sensitivity to insulin (exogenous) and increased in all patients postdialysis by an average of 57% (P < 0.01). In two patients hepatic glucose production was measured with tritiated glucose during the euglycemic clamp and declined by 84% predialysis. A similar decrease (82%) was observed postdialysis. Thus, both the hyperglycemic and euglycemic clamp techniques demonstrated tissue insensitivity to insulin to be the dominant carbohydrate defect in uremia. The surprising apparent lack of consistency in the change in beta cell response postdialysis is explained by the strong inverse correlation between beta cell sensitivity to glucose and tissue sensitivity to insulin (r = -0.920; P < 0.001). Those individuals who showed the most striking improvement in tissue sensitivity to insulin actually decreased their serum insulin response to hyperglycemia; those whose improvement in tissue sensitivity was more modest showed increases in beta cell responses.

Administration, Oral

[Genetic control of the sensitivity of Aspergillus nidulans to mutagenic factors. VII. Inheritance of cross-sensitivity to different mutagenic factors by uvs-mutants].

To study the inheritance of the sensitivity to UV, X-rays, methylmethanesulphonate (MMS), nitrosoguanidine (NG) and nitrous acid (NA) in five uvs mutants of Aspergillus nidulans, having multiple sensitivity to these factors, the sensitivity of recombinants obtained from crossing uvs mutants with uvs+ strain, resistant to all the factors analysed, and uvs leads to uvs+ revertants is investigated. Four uvs mutants (15, 17, 19 and 26) are found to have a nomogenic control of sensitivity to different mutagens. In one mutant (uvs11) the sensitivity to five factors is controlled by two non-linked mutations, one of them determining the sensitivity to UV, NG, NA, and the other--to X-rays and MMC. Phenotypic manifestations of uvs mutations is modified by cell genotype, both chromosomal and cytoplasmic factors being responsible for the modification. Phenotypic modification of uvs mutation results in the change to some (but not to all) mutagenic factors. It suggests, that not the product of uvs gene, but some other components of the reparation complex are modified. Otherwise, reparation of different DNA damages can be carried out by a single enzyme acting in different reparation complexes.

Aspergillus nidulans

Rod sensitivity relative to cone sensitivity in retinitis pigmentosa.

The present study evaluates rod sensitivity relative to cone sensitivity in retinitis pigmentosa patients. From perimetric measures of absolute thresholds to long- and short-wavelength stimuli, we find the results can be characterized in three different ways. For one group of patients it appears that only cone function is present in all parts of the visual field. For another group of patients, despite large losses in absolute sensitivity, rod sensitivity still exceeds cone sensitivity by at least the normal factor, suggesting concomitant rod and cone sensitivity losses. For a third group of patients it appears that central retinal thresholds are determined primarily by cones, midperipheral retinal thresholds determined by a composite of rod and cone function, and far- peripheral thresholds determined predominately by rods. The argument is put forward that the different groups of threshold results represent different disease mechanisms rather than different stages in the progression of a single disease process.

Adult

Synthesis of cell-impermeable Cl-sensitive fluorescent indicators with improved sensitivity and optical properties.

Quinolinium compounds have been used as Cl-sensitive fluorescent indicators in cells and cell-free membrane fractions. To improve Cl sensitivity and for conjugation via nucleophilic reaction, the compounds 6-methoxy-N-(n-aminoalkyl)quinolinium bromide hydrochloride (AAQ) with alkyl chain lengths (n) of 2 (AEQ), 3 (APQ), and 4 (ABQ) were synthesized. AAQ was water soluble, fluorescent, and quenched by Cl. The Stern-Volmer constants (KCl) for quenching of protonated AEQ, APQ and ABQ by Cl were 354, 322, and 272 M-1, respectively, higher than KCl for 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ; 118 M-1). To eliminate pH-dependent fluorescence, 6-methoxy-N-(3-trimethylammoniumpropyl)quinolinium dibromide (TMAPQ) was synthesized (KCl, 310 M-1). To red shift fluorescence excitation and emission spectra, 6-phenyl-N-(3-trimethylammoniumpropyl)quinolinium dibromide (phenyl-TMAPQ) (emission 475 nm) and N-(3-trimethylammoniumpropyl)phenanthridinium dibromide (TMAPP) (excitation 380 nm) were synthesized. AEQ and ABQ were conjugated with neutral dextran activated by cyanogen bromide to give indicator-to-dextran mole ratios of 5 to 20. KCl values at pH 7.4 were 132 (AEQ-dextran) and 237 M-1 (ABQ-dextran). To construct a single molecule with Cl-sensitive and insensitive moieties, the bichromophores 6-methoxy-N-(n- dansylsulfonamidoalkyl)quinolinium with alkyl chains of two and four were synthesized. The new Cl-sensitive indicators were used for measurement of intracellular Cl activity and for the labeling of endocytic vesicles in 3T3 fibroblasts and T84 cells. Our results indicate that N-substitution of quinoline with positively charged moieties gives increased Cl sensitivity, and extension of ring conjugation gives indicators with red-shifted fluorescence spectra.

Cell Membrane Permeability

Mutagen sensitivity of Drosophila melanogaster. III. X-linked loci governing sensitivity to methyl methanesulfonate.

Twenty-eight X-linked, recessive mutations of Drosophila melanogaster conferring enhanced sensitivity to the monofunctional alkylating agent, methyl methanesulfonate, have been recoered and assigned to five complementation groups. These groups can be distinguished on the basis of map location and variations in the pattern of mutagen sensitivity. Allelism of members of one complementation group with the previously described meiotic mutant, mei-41, (Baker and Carpenter, 1972) as well as the frequent appearance of female infertility with mutagen sensitivity suggests associated defects in meiotic chromosome behavior or early embryogenesis. Examination of the mutagen sensitivity of double mutants has led to the formulation of a working model of DNA repair for this organism. Studies of a similar nature (Boyd et al., 1976) have identified five additional X chromosome complementation groups, suggesting that the genome of Drosophila melanogaster may contain many loci involved with mutagen sensitivity. The continued isolation and characterization of conditional mutants of this type promises future insights into the mechanisms of DNA replication, DNA repair and recombination in this complex higher eucaryote.

Animals