Low-fluence Q-switched Nd:YAG 1064-nm laser versus Q-switched Nd:YAG 532-nm laser in the treatment of hyperpigmented lips: a prospective, randomized, controlled, evaluator-blinded trial.

Lip hyperpigmentation is an esthetic problem. Clinical data from controlled comparative studies is insufficient to support the efficacy of laser treatments for hyperpigmented lips. This study is aimed to compare the efficacy of low-fluence Q-switched Nd:YAG 1064-nm laser (LFQS 1064-nm) versus Q-switched Nd:YAG 532-nm laser (QS 532-nm) for the treatment of hyperpigmented lips. A randomized, controlled, evaluator-blinded study was conducted in thirty subjects. They were randomized into 2 groups. The first group was treated with five treatment sessions with a 2-week interval of LFQS 1064-nm laser while the second group was treated with a single session of QS 532-nm laser. The evaluation was conducted at baseline, 2 weeks of each post treatment, and 4 weeks after the last treatment session. The efficacy was assessed by melanin index, Methuen colored plate, photographic evaluation, pain score, patient's satisfaction, and patient's Dermatology Life Quality Index. The adverse effects were also recorded. All patients attained throughout the study protocol. The most frequent fluence applied was 2.4 J/cm2 (2.2-2.5 J/cm2) and 2.0 J/cm2 (1.7-2.4 J/cm2) in the LFQS 1064-nm group and QS 532-nm group, respectively. The results of the QS 532-nm group showed greater percentage of melanin index reduction and better average mean of photographic evaluation percentage changes from the baseline than the LFQS 1064-nm group (p < 0.001 and p < 0.001, respectively). The adverse effects were less likely to occur in the LFQS 1064-nm group. Few cases of scale, hypopigmentation, bleb formation, postinflammatory hyperpigmentation, and labial edema occurred only in the QS 532-nm group.

Evaluation of protective effect of propolis on parotid salivary glands in gamma-irradiated rats.

OBJECTIVE AND BACKGROUND: One of the most significant side effects of radiotherapy for head and neck cancers is xerostomia as a result of salivary gland damage. Considering pharmaco- logical effects of propolis, we evaluated its protective effect on salivary glands subjected to radiotherapy of head and neck cancer patients. MATERIALS AND METHODS: Twenty-one male albino rats (8-11 W, 190 ± 5 gm) were divided into three groups of seven animals. Scintigraphy was performed in all the groups. Then groups 1 (S) and 2 (SR) received normal saline injections and group 3 (PR) received propolis injection over 3 days. After that groups 2 and 3 were exposed to gamma radiation and all the rats underwent scintigraphic assessment on third day and 70th day after irradiation. The lips and tongues of rats in groups 2 and 3 were examined for mucositis daily in first 10 days. At the end, the parotid glands of all rats were examined histologically. RESULTS: Scintigraphy results of third and 70th day after irradiation showed statistically significant differences between PR and SR as well as SR and S. However, there was no significant difference between the PR and S groups. Histopathologic assessment demonstrated significant difference between SR, PR and S. CONCLUSION: These results suggest that propolis has protective effects on salivary gland function in animal models whilst it did not prevent radiation-induced histologic changes in tissues. Further investigations are needed to elucidate mechanisms of propolis actions. Clinical significance: Regarding to the results of this study, propolis may be useful in reduction xerostomia due to radiation to salivary glands and may be helpful for head and neck cancer patients.

Self-Assembly of Cellulose Nanocrystals and Organic Colored Pigments as Reinforcement Matrix of Lipstick for Enhancing SPF.

The vermilion of the human lip, covered by a skinny epithelium with little melanin, is quite susceptible to damage from ultraviolet (UV) radiation exposure. However, commercial sunscreen filters and indelible dyes used in lipsticks can cause health hazards after percutaneous absorption or accidentally oral administration. Inspired by plant pigmentation as natural filters to protect themselves against overexposure to UV, safer bio-based sunscreens of cellulose enveloped with anthocyanin (AN) were developed using bionic design. Cellulose nanocrystals (CNC), derived from acid hydrolysis of cellulose, reinforced enhancement of UV absorption and shielding properties of AN. This innovation addresses the issue that naturally sourced UV filter application to sunscreen does not achieve a desired sun protection factor (SPF) value because of the low specific extinction value (E1,1). We also stated that the diverse formula of anthocyanin sunscreen lipsticks with CNC exhibited 10 times more SPF value than AN alone. Furthermore, they possess competitive benefits such as pleasing texture, superior adhesion, impermeable, nonphototoxicity, ease of application, and removal. This work provides a promising proof-of-concept for studying the features of natural sunscreens in the design of simple, safe, efficient, and green sunscreens.

Noncoplanar Versus Coplanar Intensity-Modulated Radiation Therapy (IMRT) for Protection of the Lip and Buccal Mucosa.

OBJECTIVE: In this study, by comparing coplanar and noncoplanar intensity-modulated radiation therapy (IMRT) treatment planning in treating tongue cancer, the significance of noncoplanar fields in the protection of the lip and buccal mucosa was determined, and a reasonable solution was selected. METHODS: Forty-eight tongue cancer patients treated from June 2019 to February 2021 were selected and randomly divided into a coplanar field group and a noncoplanar field group. The mucosal dose limit changed from 15 Gy to 45 Gy for comparison of the two treatment plans. The evaluation indicators (conformal index (CI); homogeneity index (HI); D5, D50, and D98 of the target volume; and the dose of normal tissues) were calculated under different mucosal dose limits. The clinical observation of the lip and buccal mucosa of 48 cases was monitored and graded carefully according to NCI-CTCAE V4.0. Statistical analyses were performed. RESULTS: The differences in CI, HI, D98, D50 and D5 between the two groups in the target volume tended to decrease when the mucosal dose limit was less than 30 Gy, with a significant difference (P < 0.05). When the limit exceeded 30 Gy, significant differences in other indicators except CI (P < 0.05) were still noted. In normal tissue, differences in doses between the two groups existed when the mucosal limit was less than 20 Gy, with a significant difference (P < 0.05). When the limit exceeded 20 Gy, no significant difference was noted. Patients in the noncoplanar group showed significantly better results than those in the other group in terms of the radiation-related toxicity of the lip and cheek membrane(P < 0.001). CONCLUSIONS: Compared with coplanar field radiotherapy, noncoplanar field radiotherapy can effectively reduce the exposure dose to the lip and buccal mucosa. The application of noncoplanar treatment plans exhibits good clinical significance and deserves to be promoted.

Q-switched double-frequency Nd:YAG (532 nm) laser is an effective treatment for racial lip pigmentation.

INTRODUCTION: Lip darkening is a relatively common condition, especially in the Middle East and Southeast Asia. It is well documented in the literature and generally considered to be multifactorial. The presentation can be physiologic or pathologic and caused by a variety of local or systemic factors. CASE PRESENTATION: A 32-year-old female with skin type IV presented to the clinic with concerns of darkening lips with no associated symptoms or history of disease. On examination, her lips were homogenously dark brown with the upper lip slightly darker than the lower lip. OBJECTIVE: To report effectivness of Q-switched 532 nm laser for treatment of lip pigmentation. METHOD: Topical 2.5% lidocaine/prilocaine (EMLA) cream was applied 30 minutes prior to laser therapy. The region was treated with Q-switched 532 nm laser (Medlite). RESULT: Two weeks after laser treatment , threre was satisfying subjective and objective improvment in lip pigmnetation. CONCLUSION: Q-Switched 532 nm laser effectively reduces lip pigmentation after one session with minimal adverse effects and lasting results.

TKK Aparat: an environment for voice inverse filtering and parameterization.

The study of the glottal flow, the acoustic excitation for voiced speech, provides insight into the voice signal, which is of potential benefit in many disciplines. One common method for estimating the glottal flow is inverse filtering, in which the effects of the vocal tract and the lip radiation are removed from a microphone signal. This paper presents a new inverse filtering and parameterization software package, which is available under an open-source licence. It provides a user-friendly graphical interface for rapid inverse filtering and parameterization, and the algorithms and parameters can be easily re-used in other projects. The system has already proved to be useful in algorithm development, speech science research, as well as in the study of occupational voice.

Inhibitory reflexes in human perioral facial muscles: a single-motor unit study.

OBJECTIVE: To describe the reflex responses evoked by trigeminal stimulation in perioral facial motor units (MUs) in humans. METHODS: We recorded single motor units (MUs) from perioral muscles performing three movements: elevation of the upper lip (levator labii superioris muscle--LLS), protrusion of the lips (orbicularis oris muscle--OOr) and depression of the lower lip (depressor anguli oris and depressor labii inferioris muscles--DAO/DLI) with concentric needle electrodes. MUs were tested during constant voluntary activation with non-painful cutaneous electrical stimuli applied to the mental or supraorbital nerves and intraorally. Analysis was performed with peristimulus histograms and cumulative sum. RESULTS: Eighty MUs were sampled from 17 subjects. Cutaneous stimulation induced inhibition of discharge in 100% of the lip-depressor MUs, inhibition in 65-70% of LLS MUs and in 25% of OOr MUs. Mean latency of inhibition was of 35+/-12ms. Intraoral stimulation produced an equivalent percentage of inhibitory or facilitatory effects with no difference among the three muscles. CONCLUSIONS: Reflex responses to cutaneous stimulation identify a completely inhibitory (DAO/DLI), a mainly inhibitory (LLS) and a mixed (OOr) pattern in perioral muscles. SIGNIFICANCE: A purely inhibitory trigemino-facial reflex is present in lip-lowering muscles with potential use in clinical practice.

Surgery combined with topical photodynamic therapy for the treatment of squamous cell carcinoma of the lip.

Due to the unique location of the squamous cell carcinoma (SCC) of the lip, using a single method such as extended resection or radiotherapy probably causes morphological and functional defects. So we used surgery combined with topical photodynamic therapy (PDT) to treat SCC of the lip. Under local anesthesia with 5% lidocaine, the hyperplastic and ulcerative SCC of the lip were curetted and assisted by topical PDTs after surgery. The 20% 5-aminolevulinic acid cream was used as a photosensitizer and applied evenly to the surface of the tumor lesion for 4h. Then the lesion site was irradiated with a 635-nm laser at 120J/cm(2). A total of five PDTs were performed postoperatively at an interval of 2 weeks. Photos were taken before and after every PDT to compare the skin lesions, treatment effects, and side effects. A long-term follow-up was undertaken to observe tumor recurrence. After surgery combined with five topical PDTs, the SCC of the lip disappeared without the compromised morphology of the lip, significant side effects, or tumor recurrence in one-year follow-up. Surgery combined with topical PDT can reduce the excision size of tumors and play a positive role in the treatment of tumors of special locations.

The kinetics and capacity of repair of sublethal damage in mouse lip mucosa during fractionated irradiations.

The kinetics and capacity of repair of sublethal damage in mouse lip mucosa have been investigated. To assess the rate of repair 2 and 5 irradiations have been given with intervals ranging from 1 to 24 hours. It was found that the sublethal damage induced by a dose of approximately 10 Gy was fully recovered in approximately 4 hr. After a dose of 5-6 Gy, cellular repair was completed within 3 hr. The half time of repair (T1/2) was estimated to be approximately 72 min for 10 Gy and approximately 54 min for 5-6 Gy. Although these results suggest that the rate of repair is dependent on the fraction size, the possible influence of the amount of repair of sublethal radiation damage with the various fraction sizes used can not be ruled out. To evaluate the capacity of repair, a single dose, 2, 4 and 10 fractions have been given in a maximal overall time of 3 days in order to minimize the influence of repopulation. The slope of the isoeffective curve was 0.32 and the alpha/beta ratio was 8.5 Gy. This indicates that the capacity of cellular repair of lip mucosa is similar to those of other rapidly proliferating tissues but smaller than those of late responding tissues. The results of the present and other studies demonstrate that there are considerable differences in the repair characteristics between acutely and late responding tissues. These features have to be dealt with when fractionation schedules are markedly altered.

The effect of actinomycin D on radiation induced reactions of the lip mucosa of mice.

The interaction of intraperitoneally injected Actinomycin D and irradiation was investigated in the lip mucosa of NMRI mice. In this rapidly proliferating tissue, a semiquantitative assessment of possible modifications of the radiation response by a drug can be done without using lethality as an endpoint. It was shown that a single dose of 0.5 mg/kg drug given at different times between 24 hr prior to and 24 hr after single radiation doses did not effect the rate of development nor the intensity of mucosal radiation damage. With extended time intervals of 2, 3, or 7 days between both single agents, a slight increase of the lip mucosal reaction was measured. Similar results were obtained when 5 daily drug injections of 0.15 mg/kg were administered starting at day 5 after a single radiation exposure. No differences in response could be demonstrated when fractionated irradiations with intervals ranging from 1 to 24 hr were closely combined with either single or repeated drug treatments (0.5 mg/kg in total) as compared to irradiation alone. However, a slight modification of the iso-effect dose was measured when 0.5 mg/kg Actinomycin D was administered at various periods in between 2 radiation doses separated by 10 days. A maximal effect was measured with 5 daily injections of 0.15 mg/kg drug each and given at a time when proliferative capacity was high. With 0.1 mg/kg Actinomycin D per daily injection, no enhancement of the radiation injury was found. Thus, in these circumstances no influence of Actinomycin D on radiosensitivity nor on repair of sublethal damage could be demonstrated. A clear inhibitory effect on lip mucosal repopulation by the drug is evident, but only at high drug doses close to toxic concentrations.

Results of combined external irradiation and chemotherapy of bleomycin or peplomycin for squamous cell carcinomas of the lower gingiva.

PURPOSE: In Japan, the role of radiotherapy for gingival carcinomas has not been considered as a radical treatment, but only a pre and/or postoperative treatment. This study was aimed to discuss a possibility of radiotherapy for a radical treatment. In this study, radiotherapy was given as an initial treatment for squamous cell carcinomas of the lower gingiva in simultaneous combination with chemotherapy of bleomycin or peplomycin (Tokyo, Japan). METHODS AND MATERIALS: When complete regression of the tumor was obtained, subsequent surgery was postponed with or without a booster of radiotherapy of about 30 Gy until a recurrent lesion was confirmed. RESULTS: Sixty-seven percent of 100 patients with T1 or T2 had complete regression, while only 22 (35.5%) of 62 patients with T3 or T4 had complete regression. The 5-year local control rate by T classification, including the results of secondary treatments (surgery and/or radiotherapy and/or chemotherapy) for recurrent lesions, was 91% for T1, 89% for T2, 76% for T3 and 61% for T4. The 5-year local control rate according to treatment methods was 95% in the group without surgery and 86% in the group with surgery for T1 and T2 patients. The rates were 54% and 71%, respectively for T3 and T4 patients. The cause specific 5-year survival rate by stage was 75% for Stage I, 87% for Stage II, 71% for Stage III, 51% for Stage IV and 70% overall. CONCLUSION: The combination of radiotherapy and chemotherapy could be a conservative radical treatment for T1 and T2 patients with lower gingival carcinoma.

Evaluation of mouse lip mucosa reactions after combinations of cis-diammine-1,1-cyclobutanedicarboxylate platinum (II) (CBDCA) and irradiation: single and fractionated treatments.

The influence of CBDCA (JM8) on the radiation-induced mouse lip mucosal reactions has been tested. Both single and fractionated drug doses were used intraperitoneally at 60 mg/kg and 5 X 25 mg/kg respectively. A single injection of CBDCA did not alter the response to a single radiation dose, whether the drug was given at different time intervals from 24 hr prior, to 96 hr after irradiation. A concomitant treatment of daily CBDCA injections and irradiations for 5 consecutive days demonstrated no change of the capacity to repair sublethal radiation damage. When two equal sized radiation doses were separated by 10 days and CBDCA was administered daily from day 3 to 7, the ability to repopulate the lip mucosa epithelium during the radiation-free period was not influenced.

Radiosensitization produced in vivo by once- vs. twice-weekly 2'2'-difluoro-2'-deoxycytidine (gemcitabine).

PURPOSE: Gemcitabine (2'2'-difluoro-2'-deoxycytidine, dFdCyd) is a potent radiosensitizer of rodent and human tumor cells. Our Phase I clinical trial using once-weekly dFdCyd as a radiosensitizer in the treatment of patients with Stage IV squamous cell head and neck cancer has produced a high rate of tumor response and significant normal mucosal toxicity. These findings raised the question of whether we are using dFdCyd in the optimal dose and schedule. In vitro studies suggest that twice-weekly dFdCyd has the potential to be more effective than once-weekly dFdCyd when administered in combination with radiation (RT) given 5 days per week. Therefore, we have used a mouse model to assess whether the therapeutic ratio of combined modality therapy may be improved by using a twice-weekly drug regimen. We asked two questions: 1) Does a once-weekly or twice-weekly dFdCyd regimen cause more normal tissue radiosensitization? 2) Does a once-weekly or twice-weekly dFdCyd + RT regimen produce a better therapeutic index? METHODS AND MATERIALS: To assess normal tissue toxicity, C3H mice underwent mouth (60)Co RT (27.5 Gy in 5 daily fractions) +/- dFdCyd delivered intraperitoneally (IP) either once or twice weekly 6 hours prior to irradiation. Acute lip reactions were quantified according to a standard scoring system, and weight loss was measured. We measured tumor control using squamous cell carcinoma (SCC) VII murine squamous cell flank tumors (50-125 mm(3)) treated with the same regimens used in the mouth irradiation model. RESULTS: We found that dFdCyd delivered 800 mg/kg once weekly or 150 mg/kg twice weekly caused similar (and maximal tolerable) weight loss; therefore these regimens were chosen to test which schedule produced more acute lip radiosensitization. Twice-weekly dFdCyd + RT was somewhat more toxic by weight loss (800 mg/kg once weekly: 11.9%; 150 mg/kg twice weekly: 17.7%; p = 0.09). To assess therapeutic index, we treated SCC VII flank tumors with RT combined with isotoxic drug/RT regimens (dFdCyd 800 mg/kg once weekly or 100 mg/kg twice weekly). Tumors treated with twice-weekly dFdCyd + RT were significantly smaller than tumors treated with once-weekly drug + RT at 28 days from the start of treatment (p < 0.03). CONCLUSIONS: These findings demonstrate that equitoxic once- versus twice-weekly dFdCyd regimens cause differing levels of oral mucosal radiosensitization. This would suggest that each radiation-dFdCyd schedule will require its own dFdCyd dose escalation trial (which cannot be determined by the maximum tolerated dose (MTD) for dFdCyd alone using that schedule). In addition, our findings suggest that for head and neck cancers twice-weekly dFdCyd may have a higher therapeutic index compared with once-weekly dFdCyd when combined with daily RT.

Interleukin-1 modulatory effect on the action of chemotherapeutic drugs and localized irradiation of the lip, duodenum, and tumor.

PURPOSE: This study was conducted to examine the radioprotective and radiochemoprotective capabilities of interleukin 1 beta (IL-1) on two acute-reacting normal tissues of the C3H mouse, the mucosa of the lip and the duodenum. Also assessed was the modulating effect of IL-1 on tumor growth in the same strain of mice. METHODS AND MATERIALS: IL-1 was administered to C3H/Km mice in combination with fractionated irradiation, or with cyclophosphamide, cisplatin, or 5-fluorouracil (5FU) followed by irradiation. Normal tissue damage was evaluated in the mouse lip, using a subjective scoring system for tissue reaction, and in the duodenum, using the crypt cell survival assay. RIF-1 fibrosarcoma tumor response was assayed with the regrowth delay method. RESULTS: IL-1 protected against the acute reaction produced by fractionated irradiation in the lip mucosa, shifting the dose-response curve by 3.8 Gy. IL-1 was protective when injected intraperitoneally 24 hr before CY or c-DDP, which were given immediately before the first of five daily radiation dose fractions. The dose-response curves for cyclophosphamide and cisplatin were shifted 4.0 Gy and 1.6 Gy, respectively. IL-1 did not protect against 5FU toxicity when treatments were administered in that same sequence; however, when 5FU was given 4 or 8 hr before IL-1 and the first radiation dose fraction followed 20 or 16 hr later, there was significant protection and the curves were separated by 1.5 Gy or 3.5 Gy. IL-1 also protected duodenal crypt cells against the cytocidal effect of fractionated irradiation, with a dose difference of 1.5 Gy and an improvement of crypt survival of 11.7%. It was even more protective for these cells against the enhanced drug toxicity when cyclophosphamide or 5FU were administered immediately before the first of five daily radiation doses, with the dose differences of 4.4 and 5.3 Gy, respectively, and improvements of crypt survival of 33.8 and 29.9%, respectively. There was no modification by IL-1 of the effect of irradiation alone on the RIF-1 tumor. CONCLUSION: This study demonstrates the potential for use of IL-1 as an auxiliary in combinations with chemotherapeutic agents and radiation. It also indicates that for some drugs, such as 5FU, IL-1 effects may be sequence dependent.

Interleukin 1 increases thymidine labeling index of normal tissues of mice but not the tumor.

PURPOSE: This study was conducted to investigate the action of human recombinant interleukin 1 as a radioprotector for different mouse normal cells other than bone marrow cells. METHODS AND MATERIALS: Semi-continuous injections of tritiated thymidine were administered every 6 h, over 24 h to determine thymidine labeling index. Mice were injected with recombinant human interleukin 1 24 h prior to tritiated thymidine and were compared to control animals that did not receive interleukin 1. Mice were killed 1 h after the last thymidine injection. The 24 h thymidine labeling index for normal tissues and RIF-1 tumor was determined. Labeling indices were also determined 1-14 days after a series of fractionated irradiations with or without pretreatment with a single dose of interleukin 1 administered 24 h prior to the first radiation. RESULTS: The thymidine labeling index of normal tissues was higher following the injection of recombinant human interleukin 1 24 h before radiolabeling. This was found in all normal tissues tested, including the lip and tongue mucosal basal cell layers, crypt cells of the duodenum, alveolar cells of the lung, hepatocytes, and basal skin cells. The thymidine labeling index of RIF-1 fibrosarcoma was not affected by interleukin 1 injection. A single interleukin 1 injection 24 h before the first radiation fraction also increased the thymidine labeling indices of normal tissues after localized fractionated irradiation. The thymidine labeling index of RIF-1 tumor was not increased by interleukin 1 administration except after relatively high radiation doses (20 Gy in five fractions). The ability of interleukin 1 to enhance the thymidine labeling index declined after the first day following the completion of fractionated irradiation. CONCLUSION: Recombinant human interleukin 1 increased the 24 h thymidine labeling index in normal tissues in mice, but not in RIF-1 tumor. Fractionated irradiation could maintain the effect of a single dose of interleukin 1, administered 24 h prior to the first fraction, up to 24 h after the end of radiation.

Acute reactions of the lip mucosa of mice to fractionated irradiations.

The acute reaction of the lip mucosa of mice after single and fractionated irradiations has been investigated. The mouths of 24 mice were irradiated simultaneously in a single field. It was found that the acute reaction of lip mucosa can easily and reliably be scored. The variation in scoring between different observers is small and the reaction is reproducible. The mucosal reaction starts at day 7, reaches a maximum at about day 11-12 and regresses rapidly during the following 6 to 7 days. The overall reaction period is thus shorter for lip mucosa than for skin in the mouse, indicating a shorter cell cycle time. Dose-response curves can be constructed by plotting the average reaction from day 8 to 17 versus the total dose. The curve of log isoeffect dose for an average reaction level 3 against log number of fractions has a slope of 0.35 for a dose rate of 200 cGy/min and 0.29 for 33 cGy/min. The dose required to induce focal mucosa desquamation is significantly lower than that necessary to produce spotted epidermolysis in skin (16.5 Gy vs. 33 Gy for single dose).

Effect of decreasing the dose rate of irradiation on the mouse lip mucosa. Comparison with fractionated irradiations.

The effect of continuous irradiation, delivered at five different dose rates (642, 76.8, 14.1, 2.9 and 1.5 Gy.h-1), has been investigated using the mouse lip mucosa. There was a striking dose rate effect (DRE) below 14.1 Gy.h-1 while above this dose rate the DRE was relatively small. No DRE was observed between irradiations delivered at 642 and 76.8 Gy.h-1. A comparison was made with the previously published results of high dose rate (84 Gy.h-1) fractionated irradiation (2, 4, 10 and 20 fractions). For both types of irradiation treatment an alpha/beta value of 7.4 Gy and a half-time for repair of 47 min was derived.

The effect of small radiation doses per fraction on mouse lip mucosa assessed using the concept of partial tolerance.

The acute effect of small radiation doses per fraction on mouse lip mucosa was investigated in the present study. In order to minimize the amount of additional sparing by regeneration during fractionated irradiations in this rapidly proliferating tissue, the overall treatment time had to be limited to at most 4 days, so that the number of irradiations that could be delivered was limited. Therefore, the concept of partial tolerance, established in the rat spinal cord model, was applied. The present experimental data confirm the validity of using this concept for assessing the effect of small radiation doses on tissues. The results of experiments covering a wide range of fraction sizes show that the isoeffective dose for a given mucosal reaction increases when the dose per fraction is progressively decreased to about 2 Gy per fraction. Further reduction of the size of dose per fraction, however, does not result in a detectable extra increase in the total dose to produce the same level of biological effect. It seems that the dose limit of sparing by fractionation in this rapidly proliferating normal tissue might be situated at larger fraction sizes than 0.6 Gy as estimated on basis of the mathematical linear-quadratic model, using an alpha/beta ratio of 6 Gy measured from data with doses per fraction in the range of 2 to 10 Gy.

Biological equivalance of low dose rate to multifractionated high dose rate irradiations: investigations in mouse lip mucosa.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate the biological equivalence of continuous low dose rate (LDR) irradiations to multifractionated high dose rate (HDR) regimes. The applicability of the LQ model was analysed for fraction sizes and dose rates relevant for the clinic. MATERIAL AND METHODS: Investigations were performed in mouse lip mucosa. HDR fractions were given in an overall treatment time ranging from 10 h to 3.5 days. The dose rate effect was analysed in the range of 84 to 0.76 Gy/h. For an assessment of biological equivalence in comparison to LDR, HDR irradiations have been performed in the same overall treatment time as the corresponding LDR regimes. RESULTS: Recovery leads to sparing of radiation damage as the dose rate is reduced from 84 to 0.76 Gy/h (20.0 versus 45.7 Gy ED50). No significant additional sparing from 0.9 to 0.76 Gy/h could be demonstrated (44.9 versus 45.7 Gy ED50). Even 30 HDR fractions in 24 h were not sufficient to match the effect of LDR over the same time period (38.2 versus 41.1 Gy ED50). The present data give evidence for a bi-exponential repair process in mouse lip mucosa (T1/2 fast 27 min, T1/2 slow 150 min). Repair is dominated by the faster component (> 80%). CONCLUSIONS: LDR is the most efficient way to deliver radiation if recovery is to be maximised and the overall time kept as short as possible. When used with realistic parameters the LQ model is capable of providing quantitative guidelines in areas of clinical interest.

A murine model of lip epidermal/mucosal reactions to X-irradiation.

A new radiobiological test system has been developed for lip epidermal/mucosal reactions in mice. This is intended for use in investigations of the effect of non-standard fractionation and of modifying drugs on oral radiation reactions in human cancer patients. An arbitrary scale of scores was devised, with separate scores for oedema of the lips and for erythema or exudation. After single doses of 13-20 Gy, the mouse lip epidermal reactions began at 5 days, reached a peak about 10-13 days, and had fallen to low values, but not to zero, by 21 days. Several different periods for averaging the reaction scores were tested for relative steepness and variability, the most useful being 10-12 days inclusive or the 12th day score alone. The use of longer periods of averaging led to apparent saturation of the scores. It was found that large doses of X-rays repeated at 21-23 day intervals did not lead to escalating waves of reactions unless each dose was greater than 17 Gy. With these larger doses, escalation of reactions occurred even if the intervals were extended.