Hyperpigmented Macules and Patches on the Face: Exogenous Ochronosis or Lichen Planus Pigmentosus?

We present a case of a patient with a 10-year history of blue-black macules and patches on the face and an associated history of skin-lightening cream usage. The skin lightening cream contained hydroquinone, which is often associated with exogenous ochronosis (EO). Interestingly, the biopsy did not show characteristic findings of ochronosis, confusing the final diagnosis, however discontinuing the skin-lightening creams halted the progression of the patient's skin lesions supporting a diagnosis of EO. EO presents as asymptomatic hyperpigmentation after using products containing hydroquinone. This condition is most common in Black populations, likely due to the increased use of skin care products and bleaching cream containing hydroquinone in these populations. Topical hydroquinone is FDA-approved to treat melasma, chloasma, freckles, senile lentigines, and hyperpigmentation and is available by prescription only in the US and Canada. However, with the increased use of skin-lightening creams in certain populations, it is important for dermatologists to accurately recognize the clinical features of exogenous ochronosis to differentiate it from similar dermatoses. An earlier diagnosis can prevent the progression to severe presentations with papules and nodules. We summarize the clinical presentations diagnostic features, and treatment pearls, concluding with a discussion of the differential diagnoses.  J Drugs Dermatol. 2024;23(7):567-568.     doi:10.36849/JDD.8248.

The antioxidant, tert-butylhydroquinone: a new cause of asthma.

The antioxidant, tert-butylhydroquinone (TBHQ), a common additive in food and cosmetics can cause allergic contact dermatitis. A 49-year-old non-atopic male factory worker developed asthma in connection with cleaning mixing drums containing TBHQ. Due to the suspicion that TBHQ might be the cause of asthma, a specific inhalation challenge was carried out. Lactose was used as a control agent. The following day he developed asthma symptoms with a 41% drop in FEV1 after 30-min exposure to small amounts of TBHQ and water. Methacholine reactivity increased 5-fold after TBHQ exposure compared to pre-exposure reactivity. This suggests that TBHQ may be the cause of asthma in this case. Due to this case respirators were introduced in the factory to reduce TBHQ exposure. TBHQ has not previously been shown to cause asthma.

Prospective, randomized, double-blind clinical study of split-body comparison of topical hydroquinone and hexylresorcinol for skin pigment appearance.

Dyspigmentation is a common cosmetic concern in dermatology. Currently, the first line topical medication in the United States is hydroquinone. Hydroquinone use is associated with potential safety concerns including cytotoxicity to melanocytes, systemic absorption, metabolism in distant organs, and production of potentially carcinogenic metabolites. Hexylresorcinol is an ingredient that has been used in food preservation and as antiseptic has been shown to inhibit tyrosinase in vitro and has been studied as a novel skin-lightening agent. To perform a double-blind randomized split-body investigation of comparison on topical hexylresorcinol and hydroquinone on face and hands to assess for change in the appearance of skin tone and pigmentation. Thirty-two healthy female participants ages 35-65 (50.93 ± 7.37) years old with skin type I-IV were randomized to using either topical 1% hexylresorcinol or 2% hydroquinone on the left or right side of the face and corresponding hand over 12 weeks. The topical preparation was applied twice a day to assigned areas. Standardized photos were taken of the face and colorimetric measurements were taken of both sides of the forehead, cheeks and each hand at baseline (Day 0), week 4, and week 12. Of the 32 participants, 3 were lost to follow-up and the remaining were included in the final analysis. Pigmentation measured by colorimeter and clinical grading were significantly decreased at 4 and 12 weeks relative to baseline with no difference between the HR and HQ groups. No adverse effects were noted with either intervention. Hexylresorcinol 1% is well-tolerated and equivalent to hydroquinone 2% in reducing the appearance of facial and hand pigment. Further studies with an expanded population and longer time course are warranted.Registration No.: NCT04345094.

Comparison of the efficacy of cysteamine 5% cream and hydroquinone 4%/ascorbic acid 3% combination cream in the treatment of epidermal melasma.

BACKGROUND: Few safe and effective treatments are available for melasma. Cysteamine, a non-melanocytotoxic molecule is a safer alternative to hydroquinone and usable for long-term use. AIM: To evaluate the effect of cysteamine 5% cream in the treatment of melasma. METHODS: Sixty-five of 80 patients completed this single-blind, randomized, controlled trial. The patients received cysteamine 5% or hydroquinone 4%/ascorbic acid 3% (HC) cream. The therapeutic response was evaluated by modified MASI (mMASI) and melanin index (SkinColorCatch) after 2 and 4 months of treatment. The effect of treatment on the quality of life was also assessed. RESULTS: The decrease in mMASI score was from 6.69 ± 2.96 to 4.47 ± 2.16 in the cysteamine group and from 6.26 ± 3.25 to 3.87 ± 2.00 in the HC group after 4 months (p values < 0.001). The melanin index decreased from 37.72 ± 10.17 to 31.47 ± 11.90 in the cysteamine group and from 36.37 ± 10.80 to 23.16 ± 8.83 in the HC group after 4 months (p-value = 0.003 and <0.001, respectively). The difference between mMASI score at baseline and month 4 was not significant between both groups (p-value > 0.05). The difference between the melanin index at baseline and month 4 was significantly more pronounced in the HC group (p-value = 0.002). Quality of life improved in both groups (p-value < 0.05), but was not significantly different between groups (p-value > 0.05). CONCLUSION: Cysteamine was confirmed to be an effective treatment for melasma, with equivalent results to HC in reducing mMASI score and improving quality of life, despite lesser melanin index reduction observed. Cysteamine and HC efficacy was confirmed in patients recalcitrant to previous treatments, by a significant reduction of mMASI and melanin index.

Hyperpigmentation: Looking beyond hydroquinone.

Hyperpigmentation is the most common complaint in the age group 40-45 years, seeking consultation for skin disorders. Hydroquinone is a commonly used depigmenting agent in clinical practice for treating hyperpigmentation. Prolonged use of hydroquinone has been associated with cancer risk and exogenous ochronosis. The CARES (The Coronavirus Aid, Relief, and Economic Security Act) Act of 2020 has instituted significant changes to hydroquinone containing OTC (over the counter) products, and consequently, many hydroquinone-based OTC products had to be withdrawn from the market. Henceforth, products containing hydroquinone would need US Food and Drug Administration approval via new drug application pathways for commercialization. Alternative treatment options to hydroquinone in clinical practice are reviewed in this paper with regard to their safety and efficacy vis a vis hydroquinone. Also, new potential treatment options such as thiamidol, Polypodium leucotomos, and glutathione are discussed. The review shows that these alternative depigmenting agents can be rationally combined to achieve desired treatment goals in the management of hyperpigmentation.

Repigmentation by combined narrow­band ultraviolet B/adipose­derived stem cell transplantation in the mouse model: Role of Nrf2/HO­1­mediated Ca2+ homeostasis.

Vitiligo is a depigmentation disease commonly seen in clinical practice, mainly involving loss of functional epidermal pigment cells and hair follicle melanocytes. Narrow­band ultraviolet B (NB­UVB) has emerged as the first choice of treatment for vitiligo, but long­term exposure may have serious consequences. Recently, it was reported that adipose­derived stem cells (ADSCs) improve melanocyte growth and the efficacy of melanocyte transplantation. The present study aimed to examine the efficacy of NB­UVB/ADSC­transplantation combined therapy on a mouse vitiligo model and explore the underlying mechanisms by focusing on endoplasmic reticulum stress and cellular calcium (Ca2+) homeostasis. Vitiligo mice models were established by applying 40% monobenzone (MBZ) cream twice daily and treated with NB­UVB/ADSC combination therapy. Some treated mice were also given ML385, a nuclear factor erythroid 2 like 2 (Nr2) inhibitor. Histopathological changes were evaluated using a depigmentation evaluation score and observed with hematoxylin and eosin staining on skin tissues. ELISA was used to measure diagnostic markers in plasma. Flow cytometric assay was performed to quantify CD3+, CD4+ and CD8+ levels. Expression levels of associated proteins were detected with western blot and immunofluorescence. Treatment of mice with MBZ­induced depigmentation patches on the skin was accompanied with loss of redox balance and disruption of cellular Ca2+ homeostasis. Oxidative stress and Ca2+ unbalancing were improved after the mice were treated by NB­UVB/ADSCs transplantation combination therapy. ML385, strongly negated the protective effect of NB­UVB/ADSC transplantation combination therapy, indicating the critical role of Nr2 signaling. The findings improved the understanding of the pathogenesis of vitiligo and will guide future development of therapeutic strategies against it.

Efficacy and safety of topical isobutylamido thiazolyl resorcinol (Thiamidol) vs. 4% hydroquinone cream for facial melasma: an evaluator-blinded, randomized controlled trial.

BACKGROUND: Melasma can be refractory to treatment, and relapses are frequent. Thiamidol is a new potent tyrosinase inhibitor that has been found effective as a cosmeceutical for the depigmenting of melasma. OBJECTIVE: This study compared the efficacy and tolerability of topical 0.2% Thiamidol vs. 4% hydroquinone for facial melasma. METHODS: Fifty women with facial melasma participated in a randomized, evaluator-blinded, controlled study from September through November 2020. Patients were randomly assigned to apply a double layer of 0.2% Thiamidol twice a day or 4% hydroquinone cream at bedtime, for 90 days. Both groups received tinted sunscreen (sun protection factor 60, PPD 20). The primary outcome was the change from the baseline Modified Melasma Area Seve:rity Index (mMASI) score. Secondary outcomes were improvements in the patients' quality of life [Melasma Quality of Life Index (MELASQoL)], colourimetry, and Global Aesthetic Improvement Scale (GAIS) evaluation. RESULTS: One participant, from the hydroquinone group, did not complete the study (unrelated to adverse effects). The mean (SD) age of the participants was 43 (6) years, and 86% were phototypes III-IV. Both groups exhibited a reduction in mMASI, MELASQoL, and colour contrast scores (P < 0.01). The mean [95% confidence interval (CI 95%)] reductions of the mMASI scores were 43% (35-50%) for Thiamidol and 33% (23-42%) for hydroquinone. There was no difference between the groups in the reductions in mMASI, MELASQoL, colourimetric contrast and GAIS scores (P ≥ 0.09). The GAIS analysis resulted in an improvement of 84% (CI: 95% 67-97%) for participants in the Thiamidol group and 74% (CI: 95% 61-93%) for those in the hydroquinone group. There were only mild adverse effects in the Thiamidol group, but allergic contact dermatitis was evidenced in two (8%) participants. CONCLUSION: The melasma improvement achieved using 0.2% Thiamidol did not differ from that of 4% hydroquinone cream. Thiamidol can be considered a suitable option for melasma patients with poor tolerability or treatment failure with hydroquinone.

Chemical induced pathognomonic features observed in human vitiligo are mediated through miR-2909 RNomics pathway.

BACKGROUND: Chemicals like Monobenzyl Ether of Hydroquinone (MBEH) and 4-Tertiary Butyl Phenol (4-TBP) have been widely recognized to induce clinical lesions that resemble vitiligo, but exact molecular pathway through which these chemicals initiate vitiligo is still far from clear. OBJECTIVES: Since vitiligo is widely considered as an autoimmune disease, this study was an attempt to understand miR-2909 RNomics in vitiligo pathogenesis using MBEH treated primary melanocytes as an archetype cellular model because MBEH causes pathological features indistinguishable from clinical vitiligo. METHODS: Primary melanocytes were treated with MBEH and 4-TBP and the role of miR-2909 RNomics at transcriptional and translational level was explored through qRT-PCR, western blot analysis, flow cytometry, immunocytochemistry, immunohistochemistry and in silico binding affinities. 4 mm punch biopsies were also obtained from lesional sites of vitiligo patients to validate the results observed in cell culture experiments. RESULTS: MBEH induced miR-2909 RNomics led to downregulation of MITF, TYR, TYRP1, and TYRP2 leading to decreased melanin synthesis which in turn is a characteristic trait of vitiligo. On the other hand, 4-TBP increased TGF-ß which also has the intrinsic capacity to downregulate MITF leading to decreased melanin synthesis and thereby initiation of vitiligo. CONCLUSION: Based upon our results we propose a molecular pathway which has the inherent capacity to resolve the mechanism through which these chemicals may induce vitiligo. This mechanism was also found to be involved in the lesional biopsies of vitiligo patients. These results could be exploited in better understanding the pathogenesis as well as in treatment of vitiligo.

A comparative study of topical 5% cysteamine versus 4% hydroquinone in the treatment of facial melasma in women.

OBJECTIVE: To assess the efficacy and safety of topical 5% cysteamine versus 4% hydroquinone in the treatment of facial melasma in women. Topical 5% cysteamine is an antioxidant and tyrosinase inhibitor that has been shown to be effective in the treatment of melasma. However, to date, no study has compared the performance of topical cysteamine to hydroquinone for facial melasma. METHODS: A quasi-randomized, multicenter, evaluator-blinded clinical trial was conducted on 40 women with facial melasma who were submitted to the nightly application of 5% cysteamine (CYS) or 4% hydroquinone (HQ) on hyperpigmented areas for 120 days. Both groups were required to use tinted sunscreen (SPF 50; PPD 19). Subjects were assessed at the inclusion and after 60 and 120 days of treatment for mMASI, MELASQoL, and the difference in colorimetric luminosity between melasma and the adjacent unaffected skin. The Global Aesthetic Improvement Scale was used to assess the difference in the appearance of the skin through standardized photographs. RESULTS: The mean reduction of the mMASI scores was 24% for CYS and 41% for HQ (P = 0.015) at 60 days, and 38% for CYS and 53% for HQ (P = 0.017) at 120 days. The photographic evaluation revealed up to 74% improvement for both groups, without statistically significant difference between them (P = 0.087). The MELASQoL score showed a progressive decrease for both groups over time, despite the greater reduction for HQ after 120 days (P = 0.018). Colorimetric assessment disclosed progressive depigmenting in both groups, without statistically significant difference between them (P > 0.160). No severe adverse effects were identified in either group. Erythema and burning were the most important local adverse effects with cysteamine, although their frequency did not differ between groups (P > 0.170). CONCLUSION: Cysteamine proved to be safe, well-tolerated, and effective, despite its inferior performance to hydroquinone in decreasing mMASI and MELASQoL in the treatment of melasma.

Chemical and Toxicological Characterization of Vaping Emission Products from Commonly Used Vape Juice Diluents.

Recent reports have linked severe lung injuries and deaths to the use of e-cigarettes and vaping products. Nevertheless, the causal relationship between exposure to vaping emissions and the observed health outcomes remains to be elucidated. Through chemical and toxicological characterization of vaping emission products, this study demonstrates that during vaping processes, changes in chemical composition of several commonly used vape juice diluents (also known as cutting agents) lead to the formation of toxic byproducts, including quinones, carbonyls, esters, and alkyl alcohols. The resulting vaping emission condensates cause inhibited cell proliferation and enhanced cytotoxicity in human airway epithelial cells. Notably, substantial formation of the duroquinone and durohydroquinone redox couple was observed in the vaping emissions from vitamin E acetate, which may be linked to acute oxidative stress and lung injuries reported by previous studies. These findings provide an improved molecular understanding and highlight the significant role of toxic byproducts in vaping-associated health effects.

Corneal and Scleral Problems Caused by Skin-Lightening Creams.

PURPOSE: To present a case series of patients with corneal and scleral changes associated with the use of skin-lightening creams. This is the first report of corneal changes with these widely available creams. METHODS: Three patients of West African origin presented with strikingly similar skin, corneal, and scleral changes and were found to have all been using skin-lightening creams containing hydroquinone. Histopathology was obtained for 1 patient. RESULTS: Three patients were referred to the corneal clinics of 2 hospitals with corneal changes and a history of blurred vision for 1 to 3 years. There was a 60-year-old woman from Nigeria and a 68-year-old woman and a 73-year-old man both from Ghana. All 3 had been using skin-lightening lotions containing hydroquinone on their faces for between 3 and 15 years and had black-blue facial pigmentation of exogenous ochronosis, a recognized complication of these creams. Their corneas all had horizontal striae radiating across the posterior corneas with scleral thinning and plaques. Linear brown epithelial pigmentation was observed within the lower third of the corneas. Biopsy of the sclera in 1 patient showed ochronosis. CONCLUSIONS: We present previously unreported eye changes associated with the use of skin-lightening creams containing hydroquinone, with a triad of signs: posterior corneal striae radiating from 3 o'clock to 9 o'clock, thinning and plaques in the sclera, and a normal endothelial cell count. Similar pathological changes are seen in exogenous ochronosis, a recognized skin complication of hydroquinone, are seen in the sclera.

Topical silymarin versus hydroquinone in the treatment of melasma: A comparative study.

BACKGROUND: Melasma is a highly prevalent hyperpigmentation disorder with a high relapsing rate and a negative impact on the psychological state of the affected patients. The exact pathogenesis of melasma is not completely elucidated; however, ultraviolet induced oxidative stress has an important role in its pathogenesis. Silymarin, antioxidant drug, reduces the harmful effects of solar ultraviolet radiation such as inflammation, immune responses, DNA damage, and pigmentation. OBJECTIVES: To assess the efficacy and safety of topical silymarin with different concentrations (0.7% and 1.4%) versus hydroquinone 4% in the treatment of melasma. METHODS: Forty-two adult female patients with melasma were assigned to three equal groups each containing 14 patients; group1 was treated by silymarin 0.7% cream, group 2 was treated by silymarin 1.4% cream and group 3 was treated by hydroquinone 4% cream. The duration of treatment was 3 months. RESULTS: MASI score was significantly reduced in all groups at the end of third month; however, there were no significant differences in the therapeutic response between the three studied groups. No side effects were recorded with silymarin, while hydroquinone was associated with significant adverse effects. CONCLUSIONS: Silymarin cream might serve as an effective and safe treatment modality for melasma.

Efeito da exposição à hidroquinona na resposta imune adaptativa induzida pela vacina contra a influenza / Effects of hydroquinone exposure on the adaptive immune response induced by the influenza vaccine

A gripe é causada pelo vírus Influenza e é um problema de saúde pública mundial, que pode levar a problemas sérios em idosos e crianças. O Brasil implantou a vacinação anual contra influenza a partir de 1999, como ação preventiva contra a doença. A vacina é produzida pelo Instituto Butantan e contém três cepas diferentes do vírus Influenza fragmentado para induzir resposta imune adaptativa, com produção de anticorpos específicos e neutralizantes. A literatura tem mostrado que a exposição à xenobióticos com potencial imunossupressor pode comprometer a eficácia de imunizações ativas, como a imunização contra a gripe. Nosso grupo de pesquisa tem mostrado que a exposição à hidroquinona (HQ), um composto tóxico presente em altas concentrações na fumaça do cigarro, prejudica a resposta imune inata e adquirida. Assim, este trabalho avaliou o efeito da exposição à HQ sobre a resposta imune à vacinação contra influenza. Camundongos machos da linhagem C57BL/6 foram diariamente expostos à HQ (2500 ppm) ou PBS, por 1 hora, por nebulização, por um período de 8 semanas. Durante este período, foram imunizados nas semanas 6 e 8 do início das exposições, pela injeção i.m. de 100µL da vacina. Os parâmetros tóxicos e imunológicos foram avaliados 7, 35 e 70 dias após a segunda dose da vacina. A exposição à HQ não alterou o peso corpóreo dos animais e nem causou alterações morfológicas no pulmão, fígado e rins (histologia por H&E); reduziu a frequência de hemácias (11%), hematócrito (14%), hemoglobina (14%) e volume celular (4%); causou estresse oxidativo no baço (citometria de fluxo); aumentou a área dos folículos de células B no baço e linfonodomegalia (histologia por H&E). Em conjunto, os dados aqui obtidos mostram que a exposição à HQ afetou mecanismos envolvidos na gênese da imunidade ativa contra influenza. Assim, os dados deste trabalho mostram mecanismos tóxicos ainda não descritos para a HQ, e ressalta a HQ como um poluente ambiental que deve ser considerado nas avaliações de risco

The flu is a health problem worldwide which is caused by the Influenza virus and may result in severe illness in infants and the elderly. The annually vaccination against influenza was implemented in Brazil in 1999 as a preventive measure. The vaccine is produced by Butantan Institute and contains three different strains of the inactivated Influenza virus which induce the adaptive immune response along with production of specific and neutralizing antibodies. The literature has shown that exposure to immunosuppressive xenobiotics may compromise the efficacy of active immunizations, such as influenza. Our research group has shown that exposure to hydroquinone (HQ), a toxic constituent of cigarette smoke, impairs both innate and adaptive immune response. Thus, the aim of this work was to evaluate the effects of HQ on the immune response induced by the influenza vaccine. Male C57BL/6 mice were daily exposed to HQ (2500 ppm) or PBS by nebulization, for 1 hour, for 8 weeks. During the exposure period, the animals were vaccinated on weeks 6 and 8 with 100µL of the vaccine. Toxicologic and immunological parameters were assessed 7, 35 and 70 days after boost administration. HQ exposure did not alter body weight and did not cause morphological alterations in the lungs, liver and kidneys (H&E staining); reduced the frequency of erythrocytes (11%), hematocrit (14%), hemoglobin (14%) and cellular volume (4%) and caused oxidative stress on the spleen (Flow Cytometry); increased the area of B cell follicles in the spleen and increased the size of draining lymph nodes (H&E staining). Altogether, these data show that HQ exposure affected mechanisms involved in the genesis of the adaptive immune response. Thus, the data presented in this work show toxic mechanisms of HQ that have not yet been described, and it also points out HQ as an environmental pollutant which should be considered on risk assessments

Cutaneous squamous cell carcinomas (SCC) associated with cosmetic skin whitening: 8 cases reported in Senegal.

BACKGROUND: The cosmetic use of bleaching products is common among women from sub-Saharan Africa. The most frequently used products are highly potent corticosteroids (clobetasol propionate) and hydroquinone. Herein, we report 8 cases of SCC in women using skin bleaching products for cosmetic purposes. Our aim is to describe the epidemiological, clinical and pathological aspects of the carcinomas observed during the course of skin lightening. METHODS: We conducted a descriptive multicentre study from August 2005 to January 2016 in three dermatology units in Senegal. We included all patients consulting for cutaneous squamous cell carcinoma associated with skin bleaching. Sociodemographic, clinical, paraclinical and therapeutic data were recorded. RESULTS: A total of 8 female patients were included. The mean age was 48.1 years (37-63 years). Topical hydroquinone and highly potent corticosteroids were the main products used over the whole body, for an average duration of 20.3 years. No pre-neoplastic skin disease was found in our patients. The clinical aspects of tumours were as follows: cauliflower-like (n=4), ulcerated (n=3) and nodular (n=1). The average development time before consultation was 6.75 months. All the cutaneous squamous cell carcinomas were localized to lichenoid lesions or exogenous ochronotic lesions on photo-exposed areas: face (n=1), neck (n=3) or upper back (n=4). The most common histopathological type was the infiltrating form and there was one case of in situ carcinoma. The outcome was favourable in six of eight patients after surgical resection. Two deaths occurred: one through tumour recurrence and the other through haemorrhagic shock. CONCLUSIONS: From 2005 to 2016, eight cases of cutaneous squamous cell carcinomas associated with cosmetic use of bleaching products were reported in Senegal. The mechanism was not fully elucidated and further studies are necessary. These observations provide an additional argument for combating this practice and including skin bleaching among known risk factors for squamous cell carcinoma.

[Squamous cell carcinoma associated with use of skin-lightening cream]. / Carcinome épidermoïde associé à une dépigmentation volontaire.

BACKGROUND: Women widely use skin-lightening products for cosmetic purposes in sub-Saharan Africa despite numerous reported cutaneous and systemic complications. The occurrence of epidermoid carcinoma has long been reported, but only three cases have been published so far. We report the first case in Mali. PATIENTS AND METHODS: A 30-year old woman with no noteworthy medical history was seen at our outpatient center for cervical ulceration that had been present for the last 5 years. She had used cosmetic bleaching cream over a period of around ten years. Physical examination revealed extensive ulceration on the left side of her neck. Blood tests for viral hepatitis and human immunodeficiency virus were negative. The pathological examination of the skin biopsy confirmed the diagnosis of squamous cell carcinoma. After failure of the initial excision with early relapse, multiple surgical ablations were performed 3 months later. DISCUSSION: The high prevalence of skin-lightening cosmetic use contrasts with the rarity of epidermoid carcinoma in depigmented skin. However, a large chronic ulcer on uncovered parts of the upper body, particularly the neck, should prompt physicians to consider skin cancer. Appropriate preventive measures include the promotion of educational messages for the general population, the use of sun-protection devices, and routine skin biopsy for all women presenting chronic cervical ulceration after long-term use of skin-lightening products.

Bcl-2 protects TK6 cells against hydroquinone-induced apoptosis through PARP-1 cytoplasm translocation and stabilizing mitochondrial membrane potential.

B cell leukemia/lymphoma-2 (Bcl-2) suppresses apoptosis by binding the BH3 domain of proapoptotic factors and thereby regulating mitochondrial membrane potential (MMP). This study aimed to investigate the role of Bcl-2 in controlling the mitochondrial pathway of apoptosis during hydroquinone (HQ)-induced TK6 cytotoxicity. In this study, HQ, one metabolite of benzene, decreased the MMP in a concentration-dependent manner and induced the generation of reactive oxygen species (ROS), the activation of the DNA damage marker γ-H2AX, and production of the DNA damage-responsive enzyme poly(ADP-ribose)polymerase-1 (PARP-1). Exposure of TK6 cells to HQ leads to an increase in Bcl-2 and co-localization with PARP-1 in the cytoplasm. Inhibition of Bcl-2 using the BH3 mimetic, ABT-737, suppressed the PARP-1 nuclear to cytoplasm translocation and sensitized TK6 cells to HQ-induced apoptosis through depolarization of the MMP. Western blot analysis indicated that ABT-737 combined with HQ increased the levels of cleaved PARP and γ-H2AX, but significantly decreased the level of P53. Thus, ABT-737 can influence PARP-1 translocation and induce apoptosis via mitochondria-mediated apoptotic pathway, independently of P53. In addition, we found that knockdown of PARP-1 attenuated the HQ-induced production of cleaved PARP and P53. These results identify Bcl-2 as a protective mediator of HQ-induced apoptosis and show that upregulation of Bcl-2 helps to localize PARP-1 to the cytoplasm and stabilize MMP. Environ. Mol. Mutagen. 59:49-59, 2018. © 2017 Wiley Periodicals, Inc.